Disease severity in sibling pairs with type 1 Gaucher disease

The only prognostic markers in Gaucher disease, the most common lysosomal storage disorder, are young age at first symptom/sign and the presence of null/severe mutations, both being predictive of more severe phenotypes. Therefore, it would be helpful to know whether siblings with the same genotype can be expected to experience comparable phenotypic expression. All non-neuronopathic sibling pairs in our referral clinic (1993–2008) with the same genotype were included. For each pair, gender, date of birth, severity score index at presentation, age at diagnosis and first symptom/sign, presence of bone involvement, spleen status, and use of enzyme replacement therapy were tabulated. There were 90 pairs of siblings: two sets of identical twins; 24 pairs of brothers, 24 pairs of sisters, and 42 pairs of mixed gender. For all measures of disease severity used, only in sibling pairs with an older sister and a younger brother were phenotypes significantly different between siblings. Thus, this large cohort of sibling pairs with type 1 Gaucher disease confirmed that, in general, the phenotypic expression in the younger sibling will be similar enough to that of an older affected sibling that genetic counseling may use those findings in a prognostic way.