Endocrine Abstracts

Background: Gaucher disease (GD) is the most common lysosomal storage disorder. The defect is deficiency of lysosomal glucocerebrosidase (GBA), due to biallelic mutations in GBA gene, characterized by the deposition of GBA in cells of the macrophage-monocyte system.

Objective: To report clinical phenotypes of GD and correlate with GBA gene mutations, and to identify GBA gene mutation in patients diagnosed with GD in Montenegro.

Methods: Demographic and clinical phenotype was recorded for each patient in the study. The diagnosis was confirmed with low leucocyte acid beta glucosidase activity. GBA gene sequencing was performed after long range PCR for selective amplification of GBA active gene and analysis of the entire coding region.

Results: We report five patients (four male, one female) of type 1 GD. The age at diagnosis ranged from 7 to 40 years. Patients experienced delays of 1–12 years in diagnosis after onset of symptoms. Most common mode of presentation was variable degree of splenomegaly and thrombocytopenia; other symptoms included bone pain, hepatomegaly, abdominal pain and fatigue. Osteopenia was present in majority of the patients: 4/5. All patients had asymptomatic Erlenmeyer flask deformity of the distal femur. In one patient hepatitis B was diagnosed, one had Parkinsonism, and one low pulmonary diffusion capacity for carbon monoxide. On enzyme replacement therapy (ERT) the hematological and visceral parameters showed significant improvement, and no significant progression in bone mineral density was noticed. GBA gene sequencing revealed homozygosity for N370S mutation in one patient. Genotypes of other patients were N370S/55bp deletion, N370S/D409H (in two patients), and H255Q/N370S (one patient).

Conclusion: This is the first report of GD from Montenegro. N370S was the most common mutation occurred in all five patients, one patient was homozygous and others compound heterozygous. The phenotypes of GD1 encountered in Montenegro were severe but all responded well to ERT.