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Lazea C, Bucerzan S, Al-Khzouz C, Zimmermann A, Vesa ȘC, Nașcu I, Creț V, Crișan M, Asăvoaie C, Miclea D, Grigorescu-Sido P. Cardiac Manifestations in a Group of Romanian Patients with Gaucher Disease Type 1 (a Monocentric Study). Diagnostics (Basel) 2021; 11:diagnostics11060989. [PMID: 34072542 PMCID: PMC8227770 DOI: 10.3390/diagnostics11060989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/20/2021] [Accepted: 05/24/2021] [Indexed: 11/17/2022] Open
Abstract
Gaucher disease (GD), one of the most common lysosomal disorders, is characterised by clinical heterogeneity. Cardiac involvement is rare and refers to pulmonary hypertension (PH), valvular abnormalities and myocardial infiltrative damage. The aim of this study was to evaluate cardiac involvement in a group of Romanian GD patients. Phenotypic and genotypic characterisation was carried out in 69 patients with GD type 1. Annual echocardiography and electrocardiography were performed to assess pulmonary pressure, morphology and function of the valves and electrocardiographic changes. Nine patients (13%) exhibited baseline echocardiographic signs suggesting PH. Mitral regurgitation was present in 33 patients (48%) and aortic regurgitation in 11 patients (16%). One patient presented aortic stenosis. Significant valvular dysfunction was diagnosed in 10% of patients. PH was associated with greater age (p < 0.001), longer time since splenectomy (p = 0.045) and longer time between clinical onset and the start of enzyme replacing therapy (p < 0.001). Electrocardiographic changes were present in five patients (7%).
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Affiliation(s)
- Cecilia Lazea
- 1st Pediatric Discipline, Mother and Child Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Clinic Pediatrics I, Emergency Pediatric Hospital, 400370 Cluj-Napoca, Romania; (S.B.); (C.A.-K.)
- Correspondence: ; Tel.: +40-744-353-764
| | - Simona Bucerzan
- 1st Pediatric Discipline, Mother and Child Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Clinic Pediatrics I, Emergency Pediatric Hospital, 400370 Cluj-Napoca, Romania; (S.B.); (C.A.-K.)
- Department of Genetic Diseases, Emergency Pediatric Hospital, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400370 Cluj-Napoca, Romania
| | - Camelia Al-Khzouz
- 1st Pediatric Discipline, Mother and Child Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Clinic Pediatrics I, Emergency Pediatric Hospital, 400370 Cluj-Napoca, Romania; (S.B.); (C.A.-K.)
- Department of Genetic Diseases, Emergency Pediatric Hospital, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400370 Cluj-Napoca, Romania
| | - Anca Zimmermann
- 1st Clinic and Polyclinic of Internal Medicine, Medical Clinic 2, Clinic of Worms, Department of Diabetology and Endocrinology, University Medical Center, 55131 Mainz, Germany;
| | - Ștefan Cristian Vesa
- Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Ioana Nașcu
- Emergency Pediatric Hospital, 400370 Cluj-Napoca, Romania; (I.N.); (V.C.); (M.C.); (C.A.)
| | - Victoria Creț
- Emergency Pediatric Hospital, 400370 Cluj-Napoca, Romania; (I.N.); (V.C.); (M.C.); (C.A.)
| | - Mirela Crișan
- Emergency Pediatric Hospital, 400370 Cluj-Napoca, Romania; (I.N.); (V.C.); (M.C.); (C.A.)
| | - Carmen Asăvoaie
- Emergency Pediatric Hospital, 400370 Cluj-Napoca, Romania; (I.N.); (V.C.); (M.C.); (C.A.)
| | - Diana Miclea
- Department of Medical Genetics, “Iuliu Hațieganu” University of Medicine and Pharmacy, Emergency Pediatric Hospital, 400012 Cluj-Napoca, Romania;
| | - Paula Grigorescu-Sido
- Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
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Vujosevic S, Medenica S, Vujicic V, Dapcevic M, Bakic N, Yang R, Liu J, Mistry PK. Gaucher disease in Montenegro - genotype/phenotype correlations: Five cases report. World J Clin Cases 2019; 7:1475-1482. [PMID: 31363476 PMCID: PMC6656677 DOI: 10.12998/wjcc.v7.i12.1475] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 05/01/2019] [Accepted: 05/11/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The most common lysosomal storage disorder is Gaucher disease (GD). It is a deficiency of lysosomal glucocerebrosidase (GBA) due to biallelic mutations in the GBA gene, characterized by the deposition of glucocerebroside in macrophage-monocyte system cells. The report targets clinical phenotypes of GD in order to correlate them with GBA gene mutations, as well as to identify GBA gene mutation in patients in Montenegro that are diagnosed with GD.
CASES SUMMARY Five patients (4 male, 1 female) of type 1 GD (GD1) are reported. The age at diagnosis ranged from 7 to 40. Patients experienced delays of 1-12 years in diagnosis after the original onset of symptoms. The most common mode of presentation was a variable degree of splenomegaly and thrombocytopenia, while other symptoms included bone pain, hepatomegaly, abdominal pain and fatigue. Osteopenia was present in a majority of the patients: 4/5. All patients were found to have an asymptomatic Erlenmeyer flask deformity of the distal femur. On enzyme replacement therapy (ERT), the hematological and visceral parameters showed significant improvement, but no significant progression in bone mineral density was noticed. GBA gene sequencing revealed homozygosity for the N370S mutation in one patient. The genotypes of the other patients were N370S/55bp deletion, N370S/D409H (2 patients), and H255Q/N370S (1 patient).
CONCLUSION The phenotypes of the GD1 encountered in Montenegro were severe but all responded well to ERT.
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Affiliation(s)
- Snezana Vujosevic
- Department of Endocrinology, Internal Medicine Clinic, Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
| | - Sanja Medenica
- Department of Endocrinology, Internal Medicine Clinic, Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
| | - Vesko Vujicic
- Hematology Department, Internal Medicine Clinic, Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
| | - Milena Dapcevic
- Hematology Department, Internal Medicine Clinic, Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
| | - Nikola Bakic
- Hematology Department, Internal Medicine Clinic, Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
| | - Ruhua Yang
- Yale Lysosomal Disease Center and Inherited Metabolic Liver Disease Clinic, Yale University School of Medicine, New Haven, CT 06510, United States
| | - Jun Liu
- Yale Lysosomal Disease Center and Inherited Metabolic Liver Disease Clinic, Yale University School of Medicine, New Haven, CT 06510, United States
| | - Pramod K Mistry
- Yale Lysosomal Disease Center and Inherited Metabolic Liver Disease Clinic, Yale University School of Medicine, New Haven, CT 06510, United States
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Balasubramanian G, Morampudi S, Chhabra P, Gowda A, Zomorodi B. An overview of Compassionate Use Programs in the European Union member states. Intractable Rare Dis Res 2016; 5:244-254. [PMID: 27904819 PMCID: PMC5116859 DOI: 10.5582/irdr.2016.01054] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
The past decade witnessed rapid development of novel drugs and therapeutic biological agents. The marketing authorization for novel therapies is often time consuming and distressing for patients. Earlier clinical trials were the only way to access new drugs under development. However, not every patient meets the enrolment criteria, and participation is difficult for patients with life-threatening, long-lasting or seriously debilitating diseases like rare diseases. Early access programs like "Compassionate Use Program (CUP)" have generated alternative channels for such patients. The European Medical Agency provides regulations and recommendations for compassionate use, upon which every European Union (EU) member state has developed its own rules and regulations. Despite previous reviews and studies, the available information is limited and gaps exist. This literature review explores CUP in 28 EU member states. Data was collected through literature review and use of country-specific search terms from the healthcare domain. Data sources were not limited to databases and articles published in journals, but also included grey literature. The results implied that CUP was present in 20 EU member states (71%). Of 28 EU states, 18 (∼64%) had nationalized regulations and processes were well-defined. Overall, this review identified CUP and its current status and legislation in 28 EU member states. The established legislation for CUP in the EU member states suggest their willingness to adopt processes that facilitate earlier and better access to new medicines. Further research and periodic reviews are warranted to understand the contemporary and future regulatory trends in early access programs.
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Affiliation(s)
- Gayathri Balasubramanian
- FSRC, Part of phamax, Bangalore, India
- Address correspondence to: Dr. Gayathri Balasubramanian, FSRC, Part of phamax, #19, KMJ Ascend, 5th Block Koramangala, Bangalore 560095, India. E-mail:
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Doneda D, Lopes AL, Oliveira ÁR, Netto CB, Moulin CC, Schwartz IV. Gaucher disease type I: Assessment of basal metabolic rate in patients from southern Brazil. Blood Cells Mol Dis 2011; 46:42-6. [DOI: 10.1016/j.bcmd.2010.10.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2010] [Accepted: 10/10/2010] [Indexed: 10/18/2022]
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Farfel-Becker T, Futerman AH. Cellular pathogenesis in sphingolipid storage disorders: the quest for new therapeutic approaches. ACTA ACUST UNITED AC 2010. [DOI: 10.2217/clp.10.13] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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