Gaucher disease in Montenegro - genotype/phenotype correlations: Five cases report

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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“…In the first case, the main clinical features were a history of bone involvement (T4 compression fracture), thrombocytopenia, anemia, and mild hepatosplenomegaly, and her glucocerebrosidase genotype was R353W (homozygosis). These clinical features are consistent with those previously reported in five other cases of GD Type I identified recently in Montenegro ( 38 ), in which the most common presentations included a variable degree of hepatosplenomegaly and thrombocytopenia. Notably, in those five cases, there was one case of homozygosity as in our case but with a different gene involvement (N370S mutation) ( 38 ).…”

“…These clinical features are consistent with those previously reported in five other cases of GD Type I identified recently in Montenegro ( 38 ), in which the most common presentations included a variable degree of hepatosplenomegaly and thrombocytopenia. Notably, in those five cases, there was one case of homozygosity as in our case but with a different gene involvement (N370S mutation) ( 38 ). To our knowledge, in the second case, the mutation identified [1582A>G (heterozygote)] in the patient with confirmed GD-related gene mutations (heterozygous) but without a definitive diagnosis of GD has not been previously reported.…”