Possible genotype-phenotype correlations in Niemann-Pick type C patients and miglustat treatment.

ABSTRACT

BACKGROUND AND PURPOSE: Niemann-Pick type C is a rare lysosomal storage disease caused by impaired intracellular cholesterol transport. The autosomal recessive disease is caused by mutations in NPC1 or NPC2 genes. METHODS: Clinical-laboratory features, genotype-phenotype correlation and miglustat treatment response of our patients diagnosed with early infantile Niemann-Pick type C were evaluated. RESULTS: In this article, four Niemann-Pick type C patients diagnosed in the early infantile period are presented. Common features of our patients were hepatomegaly, splenomegaly, cholestasis and retardation in motor development. Patients 1 and 2 are twins, with homozygous mutation c.2776G>A p.(Ala926Thr) in NPC1 gene and severe lung involvement. Lung involvement, which is mostly associated with NPC2 gene mutation in the literature, was severe in our patients and they died early. In patients 3 and 4, there were respectively c.2972del p.(Gln991Argfs*6) mutation in NPC1 gene and c.133C>T p.(Gln45*) homozygous mutation in NPC2 gene. In these two patients, improvement in neurological findings were observed with treatment of miglustat. CONCLUSION: In our twin patients, severe lung involvement was observed. Two of our four early infantile Niemann-Pick type C patients exhibited neurological gains with miglustat treatment.