Case Report
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 26, 2019; 7(12): 1475-1482
Published online Jun 26, 2019. doi: 10.12998/wjcc.v7.i12.1475
Gaucher disease in Montenegro - genotype/phenotype correlations: Five cases report
Snezana Vujosevic, Sanja Medenica, Vesko Vujicic, Milena Dapcevic, Nikola Bakic, Ruhua Yang, Jun Liu, Pramod K Mistry
Snezana Vujosevic, Sanja Medenica, Department of Endocrinology, Internal Medicine Clinic, Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
Vesko Vujicic, Milena Dapcevic, Nikola Bakic, Hematology Department, Internal Medicine Clinic, Clinical Center of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica 81000, Montenegro
Ruhua Yang, Jun Liu, Pramod K Mistry, Yale Lysosomal Disease Center and Inherited Metabolic Liver Disease Clinic, Yale University School of Medicine, New Haven, CT 06510, United States
Author contributions: Vujosevic S, Vujicic V and Mistry PK made the study design, execution, analysis, critical discussion and final approval; Medenica S made the study design, execution, analysis, manuscript drafting, final approval; Dapcevic M, Bakic N, Yang R and Liu J made the execution, analysis, final approval.
Informed consent statement: All study participants provided informed written consent for publication of this report.
Conflict-of-interest statement: The authors declare no conflicts of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sanja Medenica, MD, MSc, Doctor, Department of Endocrinology, Internal Medicine Clinic, Clinical Center of Montenegro, Ljubljanska bb, 81000 Podgorica, Montenegro. medenicasanja@gmail.com
Telephone: +38-26-9157843
Received: November 21, 2018
Peer-review started: November 21, 2018
First decision: March 10, 2019
Revised: May 1, 2019
Accepted: May 11, 2019
Article in press: May 11, 2019
Published online: June 26, 2019
Processing time: 217 Days and 17.9 Hours
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.

Keywords: Gaucher disease; Lysosomal storage disorder; Glucocerebrosidase; GBA gene sequencing; Genotype; Case report

Core tip: This is the first report on Gaucher disease (GD) originating from Montenegro that presents clinical phenotypes of GD and glucocerebrosidase (GBA) gene mutations in patients in Montenegro that are diagnosed with GD and genotype/phenotype correlations. While GBA gene sequencing revealed a homozygosity for the N370S mutation in 1 patient, the genotypes of the other patients were N370S/55bp deletion, N370S/D409H (in 2 patients), and H255Q/N370S (1 patient). The phenotypes of the GD type 1 encountered were severe but all responded well to enzyme replacement therapy. Genetic testing for their progeny was also planned.