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Schumann A, Garbade SF, Beblo S, Gautschi M, Haas D, Hochuli M, Hoffmann G, May P, Merkel M, Scholl-Bürgi S, Thimm E, Weinhold N, Williams M, Wortmann S, Grünert SC. Kidney involvement in glycogen storage disease type I: Current knowledge and key challenges. Mol Genet Metab 2025; 144:109054. [PMID: 39954548 DOI: 10.1016/j.ymgme.2025.109054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/04/2025] [Accepted: 02/04/2025] [Indexed: 02/17/2025]
Abstract
Glycogen storage disease (GSD) type Ia (glucose-6-phosphatase deficiency) and Ib (glucose-6-phosphate transporter deficiency) are both clinically characterized by fasting hypoglycaemia and hepatomegaly. Chronic kidney disease (CKD) with loss of glomerular filtration rate and albuminuria/proteinuria is a known long-term complication of GSD I that has become less frequent with improvement of therapy over the last decades. We retrospectively investigated a cohort of 63 GSD I patients (51 GSD Ia, 12 GSD Ib, mostly adults) with a mean age of 27.8 ± 1.8 years. We performed a cross-sectional analysis of renal function, metabolic parameters, co-morbidities and medication at the time of last-follow-up. Our study shows that renal complications have become less common since standardized diet and renoprotective medications are available. CKD was only evident above the age of 25 years in our cohort and the decline in glomerular filtration rate was moderate. No patient required renal replacement therapy. Renal calcifications and kidney stones were no frequent complications. Insufficient metabolic control was a potential risk factor for proteinuria. Supportive therapy with angiotensin-converting enzyme inhibitors is not regularly used in patients suffering from (micro-) albuminuria. This study reveals that with adherence to a standardized diet and renoprotective medication, renal complications in GSD I occur later and are less severe. However, renal involvement occurs at a similar frequency to GSD cohorts studied about 20 years earlier. Since micro-albuminuria in GSD increases the risk of progression of renal disease to kidney failure, a thorough characterization of larger GSD cohorts and a better understanding of underlying pathomechanisms are needed to minimize kidney involvement in GSD I.
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Affiliation(s)
- Anke Schumann
- Children's Hospital, Department of Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Freiburg University Hospital, Freiburg, Germany.
| | - Sven F Garbade
- Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Pediatric and Adolescent Medicine, Clinic I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany
| | - Skadi Beblo
- Hospital for Children and Adolescents, Centre for Pediatric Research Leipzig (CPL), Department of Women and Child Health and Center for Rare Diseases, University Hospital, University of Leipzig, Germany
| | - Matthias Gautschi
- Swiss Reference Centre for Inborn Errors of Metabolism, Site Bern, Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics and Institute of Clinical Chemistry, Inselspital, University Hospital Bern, University of Bern, Switzerland
| | - Dorothea Haas
- Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Pediatric and Adolescent Medicine, Clinic I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany
| | - Michel Hochuli
- Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Georg Hoffmann
- Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Pediatric and Adolescent Medicine, Clinic I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany
| | - Petra May
- Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany
| | - Martin Merkel
- Endokrinologikum Hamburg, Lornsenstraße 6, 22767 Hamburg, Germany
| | - Sabine Scholl-Bürgi
- Department of Child an Adolescent Health, Paediatrics I, Medical University Innsbruck, Innsbruck, Austria
| | - Eva Thimm
- Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany
| | - Natalie Weinhold
- Natalie Weinhold, Department of Pediatric Gastroenterology, Nephrology and Metabolic Medicine, Charité-Universitätsmedizin Berlin, Germany
| | - Monika Williams
- Department of Pediatrics, Division of Pediatric Genetics and Metabolism, University of North Carolina, Chapel Hill, NC, USA
| | - Saskia Wortmann
- University Children's Hospital, Paracelsus Medical University (PMU), Salzburg, Austria
| | - Sarah C Grünert
- Children's Hospital, Department of Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Freiburg University Hospital, Freiburg, Germany
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Gümüş E, Özen H. Glycogen storage diseases: An update. World J Gastroenterol 2023; 29:3932-3963. [PMID: 37476587 PMCID: PMC10354582 DOI: 10.3748/wjg.v29.i25.3932] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/15/2023] [Accepted: 04/30/2023] [Indexed: 06/28/2023] Open
Abstract
Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization. The overall estimated GSD incidence is 1 case per 20000-43000 live births. There are over 20 types of GSD including the subtypes. This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues. GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues. However, besides liver and skeletal muscle, depending on the affected enzyme and its expression in various tissues, multiorgan involvement including heart, kidney and/or brain may be seen. Although GSDs share similar clinical features to some extent, there is a wide spectrum of clinical phenotypes. Currently, the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch. In addition to nutritional interventions, pharmacological treatment, physical and supportive therapies, enzyme replacement therapy (ERT) and organ transplantation are other treatment approaches for both disease manifestations and long-term complications. The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy. Since early diagnosis and aggressive treatment are related to better prognosis, physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia, hepatomegaly, hypertransaminasemia, hyperlipidemia, exercise intolerance, muscle cramps/pain, rhabdomyolysis, and muscle weakness. Here, we aim to provide a comprehensive review of GSDs. This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.
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Affiliation(s)
- Ersin Gümüş
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children’s Hospital, Ankara 06230, Turkey
| | - Hasan Özen
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children’s Hospital, Ankara 06230, Turkey
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Scott EM, Wenger OK, Robinson E, Colling K, Brown MF, Hershberger J, Radhakrishnan K. Glycogen storage disease type 1a in the Ohio Amish. JIMD Rep 2022; 63:453-461. [PMID: 36101819 PMCID: PMC9458600 DOI: 10.1002/jmd2.12310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 06/03/2022] [Accepted: 06/08/2022] [Indexed: 11/11/2022] Open
Abstract
Glycogen storage disease type 1a (GSD1a) is an inborn error of glucose metabolism characterized by fasting hypoglycemia, hepatomegaly, and growth failure. Late complications include nephropathy and hepatic adenomas. We conducted a retrospective observational study on a cohort of Amish patients with GSD1a. A total of 15 patients cared for at a single center, with a median age of 9.9 years (range 0.25-24 years) were included. All patients shared the same founder variant in GCPC c.1039 C > T. The phenotype of this cohort demonstrated good metabolic control with median cohort triglyceride level slightly above normal, no need for continuous overnight feeds, and a higher quality of life compared to a previous GSD cohort. The most frequent complications were oral aversion, gross motor delay, and renal hyperfiltration. We discuss our unique care delivery at a single center that cares for Amish patients with inherited disorders.
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Affiliation(s)
- Ethan M. Scott
- New Leaf Center Clinic for Special ChildrenOhioUSA
- Department of PediatricsAkron Children's HospitalAkronOhioUSA
| | - Olivia K. Wenger
- New Leaf Center Clinic for Special ChildrenOhioUSA
- Department of PediatricsAkron Children's HospitalAkronOhioUSA
| | - Elizabeth Robinson
- Department of Pediatric Gastroenterology, Hepatology, and NutritionCleveland Clinic FoundationClevelandOhioUSA
| | - Kristina Colling
- Department of Pediatric Gastroenterology, Hepatology, and NutritionCleveland Clinic FoundationClevelandOhioUSA
| | - Miraides F. Brown
- Akron Children's HospitalRebecca D Considine Research InstituteAkronOhioUSA
| | | | - Kadakkal Radhakrishnan
- Department of Pediatric Gastroenterology, Hepatology, and NutritionCleveland Clinic FoundationClevelandOhioUSA
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Xu N, Han X, Zhang Y, Huang X, Zhu W, Shen M, Zhang W, Jialin C, Wei M, Qiu Z, Zeng X. Clinical features of gout in adult patients with type Ia glycogen storage disease: a single-centre retrospective study and a review of literature. Arthritis Res Ther 2022; 24:58. [PMID: 35219330 PMCID: PMC8881853 DOI: 10.1186/s13075-021-02706-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/13/2021] [Indexed: 11/21/2022] Open
Abstract
Background This study aimed to explore the clinical features of gout in adult patients with glycogen storage disease type Ia (GSD Ia). Methods Ninety-five adult patients with GSD Ia admitted to Peking Union Medical College Hospital were retrospectively analysed. A clinical diagnosis of GSD Ia was confirmed in all patients through gene sequencing. All patients had hyperuricaemia; 31 patients complicated with gout were enrolled, and 64 adult GSD Ia patients with asymptomatic hyperuricaemia were selected as a control group during the same period. Clinical characteristics were analysed and compared between the two groups. Results Thirty-one of the 95 patients had complications of gout (median age, 25 years; 11 (35.5%) females). All 31 patients had hepatomegaly, abnormal liver function, fasting hypoglycaemia, hyperuricaemia, hyperlipaemia, and hyperlacticaemia. A protuberant abdomen, growth retardation, recurrent epistaxis, and diarrhoea were the most common clinical manifestations. Among these 31 patients, 10 patients (32.3%) had gout as the presenting manifestation and were diagnosed with GSD Ia at a median time of 5 years (range, 1–14) after the first gout flare. The median age of gout onset was 18 years (range, 10–29). Fifteen of the 31 GSD Ia-related gout patients were complicated with gouty tophi, which has an average incidence time of 2 years after the first gouty flare. The mean value of the maximum serum uric acid (SUA) was 800.5 μmol/L (range, 468–1068). The incidence of gout in adult GSD Ia patients was significantly associated with the initial age of regular treatment with raw corn starch, the proportion of urate-lowering therapy initiated during the asymptomatic hyperuricaemic stage, maximum SUA level, and mean cholesterol level. Conclusions Determination of GSD Ia should be performed for young-onset gout patients with an early occurrence of gouty tophi, especially in patients with hepatomegaly, recurrent hypoglycaemia, or growth retardation. Early detection and long-term regulatory management of hyperuricaemia, in addition to early raw corn starch and lifestyle intervention, should be emphasized for GSD Ia patients in order to maintain good metabolic control. Trial registration Retrospectively registered.
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Affiliation(s)
- Na Xu
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Xinxin Han
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Yun Zhang
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Xiaoming Huang
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Weiguo Zhu
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Min Shen
- Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Wen Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| | - Chen Jialin
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China
| | - Min Wei
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Zhengqing Qiu
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Xuejun Zeng
- Department of family medicine & Division of General Internal Medicine, Department of medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China.
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Chan YC, Liu KM, Chen CL, Ong AD, Lin CC, Yong CC, Tsai PC, Lu LS, Wu JY. Modifiable factors affecting renal preservation in type I glycogen storage disease after liver transplantation: a single-center propensity-match cohort study. Orphanet J Rare Dis 2021; 16:423. [PMID: 34635148 PMCID: PMC8507322 DOI: 10.1186/s13023-021-02026-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 09/18/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND AND AIMS Glycogen storage disease type I (GSD-I) is an autosomal recessive disorder of carbohydrate metabolism, resulting in limited production of glucose and excessive glycogen storage in the liver and kidneys. These patients are characterized by life-threatening hypoglycemia, metabolic derangements, hepatomegaly, chronic kidney disease, and failure to thrive. Liver transplantation (LT) has been performed for poor metabolic control and delayed growth. However, renal outcome was diverse in pediatric GSD patients after LT. The aim of this study was to investigate the long-term outcome of renal function in pediatric GSD-I patients after living donor LT (LDLT), and to identify modifiable variables that potentially permits LT to confer native renal preservation. METHODS The study included eight GSD-Ia and one GSD-Ib children with a median age of 9.0 (range 4.2-15.7) years at the time of LT. Using propensity score matching, 20 children with biliary atresia (BA) receiving LT were selected as the control group by matching for age, sex, pre-operative serum creatinine (SCr) and pediatric end-stage liver disease (PELD) score. Renal function was evaluated based on the SCr, estimated glomerular filtration rate (eGFR), microalbuminuria, and morphological changes in the kidneys. Comparability in long-term renal outcome in terms of anatomic and functional parameters will help to identify pre-LT factors of GSD-I that affect renal prognosis. RESULTS The clinical and biochemical characteristics of the GSD and BA groups were similar, including immunosuppressive regimens and duration of follow-up (median 15 years) after LT. Overall, renal function, including eGFR and microalbuminuria was comparable in the GSD-I and BA groups (median eGFR: 111 vs. 123 ml/min/1.73m2, P = 0.268; median urine microalbuminuria to creatinine ratio: 16.0 vs. 7.2 mg/g, P = 0.099, respectively) after LT. However, in the subgroups of the GSD cohort, patients starting cornstarch therapy at an older age (≥ 6-year-old) before transplantation demonstrated a worse renal outcome in terms of eGFR change over years (P < 0.001). In addition, the enlarged kidney in GSD-I returned to within normal range after LT. CONCLUSIONS Post-LT renal function was well-preserved in most GSD-I patients. Early initiation of cornstarch therapy before preschool age, followed by LT, achieved a good renal prognosis.
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Affiliation(s)
- Yi-Chia Chan
- Liver Transplantation Center Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83303, Taiwan
| | - Kai-Min Liu
- Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83303, Taiwan.
| | - Aldwin D Ong
- Liver Transplantation Center Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83303, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83303, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83303, Taiwan
| | - Pei-Chun Tsai
- Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan
| | - Liang-Suei Lu
- Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan
| | - Jer-Yuarn Wu
- Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
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Morita M, Kanasaki K. Sodium-glucose cotransporter-2 inhibitors for diabetic kidney disease: Targeting Warburg effects in proximal tubular cells. DIABETES & METABOLISM 2020; 46:353-361. [PMID: 32891754 DOI: 10.1016/j.diabet.2020.06.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/27/2020] [Accepted: 06/08/2020] [Indexed: 12/29/2022]
Abstract
Inhibitors of sodium-glucose cotransporter 2 (SGLT2) have undoubtedly shifted the paradigm for diabetes medicine and research and, especially, diabetic kidney disease (DKD). The pharmacological action of SGLT2 inhibitors is simply the release of glucose into urine; however, precisely how SGLT2 inhibitors contribute to the health of those with diabetes has still not been completely elucidated. Towards this end, the present review provides a novel insight into the action of SGLT2 inhibitors by highlighting a neglected fuel-burning system found in proximal tubular cells-'glycolysis'. In addition, exploring the details of the molecular mechanisms and clinical biomarkers of the organ protection conferred by SGLT2 inhibitors is now required to prepare for the next stage of clinical diabetes medicine-the 'post-SGLT2 inhibitor era'.
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Affiliation(s)
- Miwa Morita
- Department of Internal Medicine 1, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan
| | - Keizo Kanasaki
- Department of Internal Medicine 1, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Japan; Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
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Okechuku GO, Shoemaker LR, Dambska M, Brown LM, Mathew J, Weinstein DA. Tight metabolic control plus ACE inhibitor therapy improves GSD I nephropathy. J Inherit Metab Dis 2017; 40:703-708. [PMID: 28612263 DOI: 10.1007/s10545-017-0054-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 04/07/2017] [Accepted: 04/28/2017] [Indexed: 01/30/2023]
Abstract
The onset of microalbuminuria (MA) heralds the onset of glomerulopathy in patients with glycogen storage disease (GSD) type I. Unlike tubulopathy, which responds to improved metabolic control, glomerulopathy in GSD I is considered refractory to medical intervention, and it is thought to inexorably progress to overt proteinuria and renal failure. Recent reports of reduced microalbuminuria following strict adherence to therapy counter this view. In contrast to type Ia, little is known regarding the prevalence of kidney disease in GSD Ib, 0, III, VI, and IX. Subjects were evaluated with 24-h urine collections between 2005 and 2014 as part of a longitudinal study of the natural history of GSD. ACE inhibitor therapy (AIT) was commenced after documentation of microalbuminuria. Elevated urine albumin excretion was detected in 23 of 195 GSD Ia patients (11.7%) and six of 45 GSD Ib (13.3%). The median age of onset of microalbuminuria in GSD Ia was 24 years (range 9-56); in GSD Ib it was 25 years (range 20-38). Of 14 with GSD Ia who complied with dietary and AIT during the study period, microalbuminuria decreased in 11, in whom metabolic control improved. All 135 patients with the ketotic forms of GSD (0, III, VI and IX) consistently had normal microalbumin excretion. Strict adherence to dietary therapy and maintenance of optimal metabolic control is necessary to halt the progression of GSD Ia glomerulopathy in patients treated with AIT. With optimal care, protein excretion can be reduced and even normalize.
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Affiliation(s)
- Gyongyi O Okechuku
- Division of Pediatric Nephrology, University of Florida, Gainesville, FL, USA
| | | | - Monika Dambska
- Glycogen Storage Disease Program, University of Florida, Gainesville, FL, USA
- Glycogen Storage Disease Program, Connecticut Children's Medical Center, 282 Washington Street, Hartford, CT, 06106, USA
| | - Laurie M Brown
- Glycogen Storage Disease Program, University of Florida, Gainesville, FL, USA
| | - Justin Mathew
- Glycogen Storage Disease Program, University of Florida, Gainesville, FL, USA
| | - David A Weinstein
- Glycogen Storage Disease Program, University of Florida, Gainesville, FL, USA.
- Glycogen Storage Disease Program, Connecticut Children's Medical Center, 282 Washington Street, Hartford, CT, 06106, USA.
- Glycogen Storage Disease Program, University of Connecticut School of Medicine, Farmington, CT, USA.
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Ete T, Roy A, Bhattacharya PK, Mishra A, Khonglah Y, Mishra J, Dorjee R, Lyngdoh M. Glycogen storage disease type 1a presenting as gouty arthritis in a young female without hypoglycaemia. THE EGYPTIAN RHEUMATOLOGIST 2016. [DOI: 10.1016/j.ejr.2015.11.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med 2015; 16:e1. [PMID: 25356975 DOI: 10.1038/gim.2014.128] [Citation(s) in RCA: 293] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 08/12/2014] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Glycogen storage disease type I (GSD I) is a rare disease of variable clinical severity that primarily affects the liver and kidney. It is caused by deficient activity of the glucose 6-phosphatase enzyme (GSD Ia) or a deficiency in the microsomal transport proteins for glucose 6-phosphate (GSD Ib), resulting in excessive accumulation of glycogen and fat in the liver, kidney, and intestinal mucosa. Patients with GSD I have a wide spectrum of clinical manifestations, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Individuals with GSD type Ia typically have symptoms related to hypoglycemia in infancy when the interval between feedings is extended to 3–4 hours. Other manifestations of the disease vary in age of onset, rate of disease progression, and severity. In addition, patients with type Ib have neutropenia, impaired neutrophil function, and inflammatory bowel disease. This guideline for the management of GSD I was developed as an educational resource for health-care providers to facilitate prompt, accurate diagnosis and appropriate management of patients. METHODS A national group of experts in various aspects of GSD I met to review the evidence base from the scientific literature and provided their expert opinions. Consensus was developed in each area of diagnosis, treatment, and management. RESULTS This management guideline specifically addresses evaluation and diagnosis across multiple organ systems (hepatic, kidney, gastrointestinal/nutrition, hematologic, cardiovascular, reproductive) involved in GSD I. Conditions to consider in the differential diagnosis stemming from presenting features and diagnostic algorithms are discussed. Aspects of diagnostic evaluation and nutritional and medical management, including care coordination, genetic counseling, hepatic and renal transplantation, and prenatal diagnosis, are also addressed. CONCLUSION A guideline that facilitates accurate diagnosis and optimal management of patients with GSD I was developed. This guideline helps health-care providers recognize patients with all forms of GSD I, expedite diagnosis, and minimize adverse sequelae from delayed diagnosis and inappropriate management. It also helps to identify gaps in scientific knowledge that exist today and suggests future studies.
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Clar J, Gri B, Calderaro J, Birling MC, Hérault Y, Smit GPA, Mithieux G, Rajas F. Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy. Kidney Int 2014; 86:747-56. [PMID: 24717294 DOI: 10.1038/ki.2014.102] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 01/27/2014] [Accepted: 02/13/2014] [Indexed: 12/18/2022]
Abstract
Renal failure is a major complication that arises with aging in glycogen storage disease type 1a and type 1b patients. In the kidneys, glucose-6 phosphatase catalytic subunit (encoded by G6pc) deficiency leads to the accumulation of glycogen, an effect resulting in marked nephromegaly and progressive glomerular hyperperfusion and hyperfiltration preceding the development of microalbuminuria and proteinuria. To better understand the end-stage nephropathy in glycogen storage disease type 1a, we generated a novel kidney-specific G6pc knockout (K-G6pc(-/-)) mouse, which exhibited normal life expectancy. After 6 months, K-G6pc(-/-) mice showed glycogen overload leading to nephromegaly and tubular dilation. Moreover, renal accumulation of lipids due to activation of de novo lipogenesis was observed. This led to the activation of the renin-angiotensin system and the development of epithelial-mesenchymal transition process and podocyte injury by transforming growth factor β1 signaling. The K-G6pc(-/-) mice developed microalbuminuria caused by the impairment of the glomerular filtration barrier. Thus, renal G6pc deficiency alone is sufficient to induce the development of the early-onset nephropathy observed in glycogen storage disease type 1a, independent of the liver disease. The K-G6pc(-/-) mouse model is a unique tool to decipher the molecular mechanisms underlying renal failure and to evaluate potential therapeutic strategies.
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Affiliation(s)
- Julie Clar
- 1] Institut National de la Santé et de la Recherche Médicale, U855, Lyon, France [2] Université de Lyon, Lyon, France [3] Université Lyon 1, Villeurbanne, France
| | - Blandine Gri
- 1] Institut National de la Santé et de la Recherche Médicale, U855, Lyon, France [2] Université de Lyon, Lyon, France [3] Université Lyon 1, Villeurbanne, France
| | - Julien Calderaro
- Département de Pathologie, Hôpital Henri Mondor, Créteil, France
| | - Marie-Christine Birling
- Institut Clinique de la Souris, Phenomin IGBMC, CNRS, Université de Strasbourg INSERM, U964, Illkirch, France
| | - Yann Hérault
- Institut Clinique de la Souris, Phenomin IGBMC, CNRS, Université de Strasbourg INSERM, U964, Illkirch, France
| | - G Peter A Smit
- Universitair Medisch Centrum Groningen, Groningen, The Netherlands
| | - Gilles Mithieux
- 1] Institut National de la Santé et de la Recherche Médicale, U855, Lyon, France [2] Université de Lyon, Lyon, France [3] Université Lyon 1, Villeurbanne, France
| | - Fabienne Rajas
- 1] Institut National de la Santé et de la Recherche Médicale, U855, Lyon, France [2] Université de Lyon, Lyon, France [3] Université Lyon 1, Villeurbanne, France
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Glycogen Storage Disease type 1a - a secondary cause for hyperlipidemia: report of five cases. J Diabetes Metab Disord 2013; 12:25. [PMID: 23738826 PMCID: PMC3937210 DOI: 10.1186/2251-6581-12-25] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2012] [Accepted: 05/27/2013] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIMS Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder, caused by deficient activity of glucose-6-phosphatase-α. It produces fasting induced hypoglycemia and hepatomegaly, usually manifested in the first semester of life. Besides, it is also associated with growth delay, anemia, platelet dysfunction, osteopenia and sometimes osteoporosis. Hyperlipidemia and hyperuricemia are almost always present and hepatocellular adenomas and renal dysfunction frequent late complications. METHODS The authors present a report of five adult patients with GSD Ia followed in internal medicine appointments and subspecialties. RESULTS Four out of five patients were diagnosed in the first 6 months of life, while the other one was diagnosed in adult life after the discovery of hepatocellular adenomas. In two cases genetic tests were performed, being identified the missense mutation R83C in one, and the mutation IVS4-3C > G in the intron 4 of glucose-6-phosphatase gene, not previously described, in the other. Growth retardation was present in 3 patients, and all of them had anemia, increased bleeding tendency and hepatocellular adenomas; osteopenia/osteoporosis was present in three cases. All but one patient had marked hyperlipidemia and hyperuricemia, with evidence of endothelial dysfunction in one case and of brain damage with refractory epilepsy in another case. Proteinuria was present in two cases and end-stage renal disease in another case. There was a great variability in the dietary measures; in one case, liver transplantation was performed, with correction of the metabolic derangements. CONCLUSIONS Hyperlipidemia is almost always present and only partially responds to dietary and drug therapy; liver transplantation is the only definitive solution. Although its association with premature atherosclerosis is rare, there have been reports of endothelial dysfunction, raising the possibility for increased cardiovascular risk in this group of patients. Being a rare disease, no single metabolic center has experience with large numbers of patients and the recommendations are based on clinical experience more than large scale studies.
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Current status of hepatic glycogen storage disease in Japan: clinical manifestations, treatments and long-term outcomes. J Hum Genet 2013; 58:285-92. [DOI: 10.1038/jhg.2013.17] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Dick J, Kumar N, Horsfield C, Jayawardene S. AA Amyloidosis in a patient with glycogen storage disorder and progressive chronic kidney disease. Clin Kidney J 2012; 5:559-61. [PMID: 26069801 PMCID: PMC4400565 DOI: 10.1093/ckj/sfs143] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Accepted: 09/14/2012] [Indexed: 12/20/2022] Open
Abstract
Type 1 glycogen storage diseases (GSD) are inherited metabolic diseases caused by defects in the activity of the glucose-6-phosphate transporter. We present the case of a 40-year-old male with glycogen storage disease type 1b (GSD1b) who was referred to our nephrology service for evaluation of his chronic kidney disease and found to have AA amyloid deposition on renal biopsy. Amyloid is a described complication of GSD1b. As the treatment of GSD has improved, patients are surviving longer and are now presenting more frequently to adult services. It is important that clinicians are aware of the possible renal complications of GSD1b.
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Affiliation(s)
- Jonathan Dick
- Renal Unit , King's College Hospital NHS Foundation Trust , Denmark Hill, London , UK
| | - Nicola Kumar
- Renal Unit , Guy's and St Thomas's NHS Foundation Trust , London , UK
| | - Catherine Horsfield
- Department of Histopathology , Guy's and St Thomas's NHS Foundation Trust , London , UK
| | - Satish Jayawardene
- Renal Unit , King's College Hospital NHS Foundation Trust , Denmark Hill, London , UK
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Martens DHJ, Rake JP, Navis G, Fidler V, van Dael CML, Smit GPA. Renal function in glycogen storage disease type I, natural course, and renopreservative effects of ACE inhibition. Clin J Am Soc Nephrol 2009; 4:1741-6. [PMID: 19808227 DOI: 10.2215/cjn.00050109] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Renal failure is a major complication in glycogen storage disease type I (GSD I). We studied the natural course of renal function in GSD I patients. We studied differences between patients in optimal and nonoptimal metabolic control and possible renoprotective effects of angiotensin converting enzyme inhibition. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Thirty-nine GSD I patients that visited our clinic were studied. GFR and effective renal plasma flow (ERPF) were measured by means of I(125) iothalamate and I(131) hippuran clearance and corrected for body surface area. Microalbuminuria was defined as >2.5 mg albumin/mmol creatinine and proteinuria as >0.2 g protein per liter. Optimal metabolic control was present when blood glucoses were >3.5 mmol/L, urine lactate/creatinine ratios <0.06 mmol/mmol, triglycerides <6.0 mmol/L, and uric acid concentrations <450 micromol/L. RESULTS Quadratic regression analysis showed a biphasic pattern in the course of GFR and ERPF related to age. Microalbuminuria was observed significantly less frequently in the patients with optimal metabolic control compared with the patients with nonoptimal metabolic control. A significant decrease in GFR was observed after starting ACE inhibition. CONCLUSIONS This study describes a biphasic pattern of the natural course of GFR and ERPF in GSD I patients, followed by the development of microalbuminuria and proteinuria. Optimal metabolic control has a renoprotective effect on the development of microalbuminuria and proteinuria in GSD I patients. Treatment with ACE inhibitors significantly decreases the GFR, especially in GSD I patients with glomerular hyperfiltration.
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Affiliation(s)
- Daniëlle H J Martens
- University Medical Center Groningen, Department of Pediatrics, Hanzeplein 1, PO Box 30 001, 9700 RB Groningen, The Netherlands.
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Reddy SK, Austin SL, Spencer-Manzon M, Koeberl DD, Clary BM, Desai DM, Smith AD, Kishnani PS. Liver transplantation for glycogen storage disease type Ia. J Hepatol 2009; 51:483-90. [PMID: 19596478 DOI: 10.1016/j.jhep.2009.05.026] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2009] [Revised: 04/04/2009] [Accepted: 05/15/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND/AIMS Hepatocellular carcinoma (HCC) most often occurs within hepatocellular adenomas (HCAs) in glycogen storage disease Ia (GSD Ia) patients. The objective of this retrospective study is to assess outcomes after liver transplantation (LT) for GSD Ia where the principal indication for transplantation was prevention of HCC. METHODS Petitions to the United Network for Organ Sharing region 11 review board for additional model for end-stage liver disease listing points were made on behalf of GSD Ia patients. Demographics, pre-operative comorbidity, and outcomes for GSD Ia patients who underwent LT were reviewed. RESULTS Between 2004 and 2006, five GSD Ia patients underwent LT. Multiple HCAs with focal hemorrhage and/or necrosis but without histological evidence of malignancy were identified in all explanted specimens. Four of five patients had complications after LT, including cytomegalovirus (CMV) infections and steroid responsive allograft rejection. Hemoglobin levels and serum triglyceride, total cholesterol, blood glucose, and lactic acid concentrations improved in all patients after LT. Corn starch feeding was not required in any patient after LT. Renal function worsened in three patients despite modifications to primary immunosuppressive medications. All patients are alive at last follow-up (range 25-48 months) and all post-transplant complications have resolved. CONCLUSIONS By removing all possible adenomatous tissue and reversing the underlying hepatic enzymatic deficiency, LT provides definitive prevention against HCC and correction of most metabolic derangements in GSD Ia patients. Renal dysfunction secondary to GSD Ia persists--underscoring the need for further studies to better understand the mechanisms of renal dysfunction in these patients.
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Affiliation(s)
- Srinevas K Reddy
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
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Martens DH, Rake JP, Schwarz M, Ullrich K, Weinstein DA, Merkel M, Sauer PJ, Smit GPA. Pregnancies in glycogen storage disease type Ia. Am J Obstet Gynecol 2008; 198:646.e1-7. [PMID: 18241814 DOI: 10.1016/j.ajog.2007.11.050] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2007] [Revised: 09/21/2007] [Accepted: 11/26/2007] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Reports on pregnancies in women with glycogen storage disease type Ia (GSD-Ia) are scarce. Because of improved life expectancy, pregnancy is becoming an important issue. We describe 15 pregnancies by focusing on dietary treatment, biochemical parameters, and GSD-Ia complications. STUDY DESIGN Carbohydrate requirements (milligrams per kilogram per minute), triglyceride and uric acid levels, liver ultrasonography, and creatinine clearance were investigated before, during, and after pregnancy. Data from the newborn infants were obtained from the records. RESULTS In the first trimester, a significant increase in carbohydrate requirements was observed (P = .007). Most patients had acceptable triglyceride and uric acid levels during pregnancy. No increase in size or number of adenomas was seen. In 3 of 4 patients, a decrease in glomerular filtration rate was observed after pregnancy. In 3 pregnancies, lactic acidosis developed during delivery with severe multiorgan failure in 1. All but 1 of the children are healthy and show good psychomotor development. CONCLUSION Successful pregnancies are possible in patients with GSD-Ia, although specific GSD-Ia-related risks are present.
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Ozen H. Glycogen storage diseases: new perspectives. World J Gastroenterol 2007; 13:2541-2553. [PMID: 17552001 PMCID: PMC4146814 DOI: 10.3748/wjg.v13.i18.2541] [Citation(s) in RCA: 174] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2007] [Revised: 03/30/2007] [Accepted: 03/31/2007] [Indexed: 02/06/2023] Open
Abstract
Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type IIIa involves both the liver and muscle, and IIIb solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and VII involve only the muscle.
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Affiliation(s)
- Hasan Ozen
- Division of Gastroenterology, Hepatology and Nutrition, Hacettepe University Children's Hospital, Ankara, Turkey.
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Lin CC, Tsai JD, Lin SP, Lee HC. Renal sonographic findings of type I glycogen storage disease in infancy and early childhood. Pediatr Radiol 2005; 35:786-91. [PMID: 15906024 DOI: 10.1007/s00247-005-1478-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2005] [Revised: 03/16/2005] [Accepted: 03/21/2005] [Indexed: 02/04/2023]
Abstract
BACKGROUND Type I glycogen storage disease (GSD-I) is an inherited disorder affecting glycogenolysis and gluconeogenesis. The characteristic manifestations are hepatomegaly, hypoglycemia, hyperlacticacidemia, hyperuricemia, and hyperlipidemia. Renal disease is regarded as a long-term complication and is reported mainly in older patients. OBJECTIVE We report the renal manifestations and renal ultrasonographic findings of GSD-I in infancy and early childhood in order to assess the role of renal sonography in the diagnosis of GSD-I. MATERIALS AND METHODS We retrospectively reviewed our hospital's database for patients with GSD-I from January 1993 to September 2004. The records of five patients were reviewed for this study. These five patients were diagnosed when they were younger than 3 years old. Data extracted from the charts included the initial extrarenal and renal manifestations, laboratory data, and imaging studies. We analyzed the indications for, and results of, renal sonography. RESULTS In addition to the clinical presentations and laboratory abnormalities, all five children had nephromegaly and increased echogenicity on ultrasonography on their first visit, although only a minor degree of tubular dysfunction was noted clinically. Three of these five patients had nephrocalcinosis or renal stones or both. CONCLUSION Hyperechoic large kidneys, nephrocalcinosis, and renal stones are common in GSD-I. They can be present in early infancy. Abnormalities on renal sonography might suggest GSD-I in a patient with suspected inborn errors of metabolism.
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Affiliation(s)
- Chun-Chen Lin
- Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
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Guidelines for management of glycogen storage disease type I - European Study on Glycogen Storage Disease Type I (ESGSD I). Eur J Pediatr 2002. [PMID: 12373584 DOI: 10.1007/bf02680007] [Citation(s) in RCA: 106] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
UNLABELLED Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods of dietary and pharmacological treatment. Based on the data of the European Study on Glycogen Storage Disease Type I, discussions within this study group, discussions with the participants of the international SHS-symposium 'Glycogen Storage Disease Type I and II: Recent Developments, Management and Outcome' (Fulda, Germany; 22-25th November 2000) and on data from the literature, guidelines are presented concerning: (1). diagnosis, prenatal diagnosis and carrier detection; (2). (biomedical) targets; (3). recommendations for dietary treatment; (4). recommendations for pharmacological treatment; (5). metabolic derangement/intercurrent infections/emergency treatment/preparation elective surgery; and (6). management of complications (directly) related to metabolic disturbances and complications which may develop with ageing and their follow-up. CONCLUSION In this paper guidelines for the management of GSD I are presented.
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Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit GPA. Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). Eur J Pediatr 2002. [PMID: 12373567 DOI: 10.1007/bf02679990] [Citation(s) in RCA: 184] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
UNLABELLED Glycogen storage disease type I (GSD I) is a relatively rare metabolic disease and therefore, no metabolic centre has experience of large numbers of patients. To document outcome, to develop guidelines about (long-term) management and follow-up, and to develop therapeutic strategies, the collaborative European Study on GSD I (ESGSD I) was initiated. This paper is a descriptive analysis of data obtained from the retrospective part of the ESGSD I. Included were 231 GSD Ia and 57 GSD Ib patients. Median age of data collection was 10.4 years (range 0.4-45.4 years) for Ia and 7.1 years (0.4-30.6 years) for Ib patients. Data on dietary treatment, pharmacological treatment, and outcome including mental development, hyperlipidaemia and its complications, hyperuricaemia and its complications, bleeding tendency, anaemia, osteopenia, hepatomegaly, liver adenomas and carcinomas, progressive renal disease, height and adult height, pubertal development and bone maturation, school type, employment, and pregnancies are presented. Data on neutropenia, neutrophil dysfunction, infections, inflammatory bowel disease, and the use of granulocyte colony-stimulating factor are presented elsewhere (Visser et al. 2000, J Pediatr 137:187-191; Visser et al. 2002, Eur J Pediatr DOI 10.1007/s00431-002-1010-0). CONCLUSION there is still wide variation in methods of dietary and pharmacological treatment of glycogen storage disease type I. Intensive dietary treatment will improve, but not correct completely, clinical and biochemical status and fewer patients will die as a direct consequence of acute metabolic derangement. With ageing, more and more complications will develop of which progressive renal disease and the complications related to liver adenomas are likely to be two major causes of morbidity and mortality.
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Affiliation(s)
- Jan Peter Rake
- Department of Paediatrics, Beatrix Children's Hospital, University Hospital Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
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Wolfsdorf JI, Holm IA, Weinstein DA. Glycogen storage diseases. Phenotypic, genetic, and biochemical characteristics, and therapy. Endocrinol Metab Clin North Am 1999; 28:801-23. [PMID: 10609121 DOI: 10.1016/s0889-8529(05)70103-1] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The glycogen storage diseases are caused by inherited deficiencies of enzymes that regulate the synthesis or degradation of glycogen. In the past decade, considerable progress has been made in identifying the precise genetic abnormalities that cause the specific impairments of enzyme function. Likewise, improved understanding of the pathophysiologic derangements resulting from individual enzyme defects has led to the development of effective nutritional therapies for each of these disorders. Meticulous adherence to dietary therapy prevents hypoglycemia, ameliorates the biochemical abnormalities, decreases the size of the liver, and results in normal or nearly normal physical growth and development. Nevertheless, serious long-term complications, including nephropathy that can cause renal failure and hepatic adenomata that can become malignant, are a major concern in GSD-I. In GSD-III, the risk for hypoglycemia diminishes with age, and the liver decreases in size during puberty. Cirrhosis develops in some adult patients, and progressive myopathy and cardiomyopathy occur in patients with absent GDE activity in muscle. It remains unclear whether these complications of glycogen storage disease can be prevented by dietary therapy. Glycogen storage diseases caused by lack of phosphorylase activity are milder disorders with a good prognosis. The liver decreases in size, and biochemical abnormalities disappear by puberty.
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Affiliation(s)
- J I Wolfsdorf
- Department of Pediatrics, Harvard Medical School, Boston, Massachussetts, USA
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Wolfsdorf JI, Laffel LM, Crigler JF. Metabolic control and renal dysfunction in type I glycogen storage disease. J Inherit Metab Dis 1997; 20:559-68. [PMID: 9266393 DOI: 10.1023/a:1005346824368] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
This study was undertaken to determine the effect on renal function of continuous glucose therapy from early childhood. Twenty-three subjects, median age 13.9 years, range 5.9-26.9 years, with type I glycogen storage disease (GSDI) treated with continuous glucose therapy from a median age of 1.3 years, range 0.1-12.9 years, had 24 h monitoring of metabolites and glucoregulatory hormones on their home feeding regimen to assess metabolic control at approximately yearly intervals for a median duration of 8 years. During the most recent evaluation, 24 h urinary albumin excretion rate (AER), kidney size, and creatinine clearance (Ccr) were measured. CCr was unrelated to age and was increased (> 2.33 ml/s per 1.73 m2) in 10/23 (43%). Mean kidney length exceeded 2SD in 16/23 (70%). AER was normal in all five subjects < 10 years and was increased (> 10 micrograms/min) in 8/23 (35%), all > 10 years of age. AER was significantly greater in subject of similar age who started continuous glucose therapy later in childhood and was significantly higher in subjects with lower mean 24 h plasma glucose concentrations and higher mean 24 h blood lactate concentrations, both at the time of assessment of renal function and over the preceding 5 years. GSDI subjects with persistently elevated concentrations of blood lactate, serum lipids and uric acid are at increased risk of nephropathy. Optimal dietary therapy instituted early in life may delay, prevent, or slow the progression of renal disease.
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Affiliation(s)
- J I Wolfsdorf
- Department of Medicine (Division of Endocrinology), Children's Hospital, Boston, MA 02115, USA
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Lim PS, Kho B. Renal disease in an adult patient with type I glycogen storage disease. Ren Fail 1995; 17:769-74. [PMID: 8771251 DOI: 10.3109/08860229509037646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
A 26-year-old Chinese male patient with type I glycogen storage disease presented with chronic renal disease, proteinuria, and urolithiasis. On renal biopsy, focal glomerular sclerosis, increased mesangial matrix and cellularity, interstitial fibrosis, tubular atrophy, and prominent arteriosclerosis were observed. Immunofluorescence microscopy revealed Ig A deposits predominantly in the glomerular mesangium. The possible mechanisms of renal involvement in glycogen storage disease are briefly discussed.
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Affiliation(s)
- P S Lim
- Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan, ROC
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Brix AE, Howerth EW, McConkie-Rosell A, Peterson D, Egnor D, Wells MR, Chen YT. Glycogen storage disease type Ia in two littermate Maltese puppies. Vet Pathol 1995; 32:460-5. [PMID: 8578635 DOI: 10.1177/030098589503200502] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Glycogen storage disease type Ia (GSD-Ia) (von Gierke's disease) was identified in two 47-day-old littermate Maltese puppies. The puppies were presented for necropsy with a history of failure to thrive, mental depression, and poor body condition. Gross findings included small body size and emaciation (212 and 246 g versus 595 g for normal littermate), severely enlarged pale livers (48 and 61 g), and pale kidneys. Histologically, there was marked diffuse vacuolation of hepatocytes with large amounts of glycogen and small amounts of lipid. Renal tubular epithelium was mildly to moderately vacuolated. Soft tissue mineralization was present in renal tubules and pulmonary alveolar septa. Biochemical analysis showed that levels of glucose-6-phosphatase were markedly reduced in liver (0.3 and 0.4 microM/minute/g tissue versus 4.7 +/- 1.5 microM/minute/g tissue for controls) and kidney (0.45 and 0.4 microM/minute/g tissue versus 4.1 microM/minute/g tissue for controls) and that glycogen content was increased in liver (9.4% and 9.4% versus 1.3% +/- 1.4% for controls). This is the first confirmed report of animals with glycogen storage disease type Ia.
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Affiliation(s)
- A E Brix
- Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, USA
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