Clinical Neuroscience

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

ÇAKAR Emel Nafiye1, ÖNAL Hasan2

MARCH 30, 2021

Clinical Neuroscience - 2021;74(03-04)

DOI: https://doi.org/10.18071/isz.74.0139

Case Reports

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. Clinical-laboratory features, genotype-phenotype correlation and miglustat treatment response of our patients diagnosed with early infantile Niemann-Pick type C were evaluated. 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. 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.

AFFILIATIONS

  1. Division of Pediatric Metabolism, University of Health Sciences, Okmeydanı Training and Research Hospital, İstanbul, Turkey
  2. Division of Pediatric Metabolism, University of Health Sciences, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul, Turkey

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