Abstract
BackgroundNiemann–Pick disease type C (NPC) is an autosomal recessive, neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. Mutations in these genes are associated with abnormal endosomal–lysosomal trafficking, resulting in the accumulation of tissue-specific lipids in lysosomes.MethodsWe described sixteen patients with NPC diagnosed between the age of 1 month and 30 years at two tertiary care centers in Palestine. The clinical phenotype, brain magnetic resonance imaging (MRI), and molecular genetic analysis data were reviewed.ResultsThe diagnosis was confirmed by molecular analysis in all patients. Fourteen out of sixteen patients were homozygous for the NPC1 p.G992W variant. Among them, most were categorized as having the late-infantile neurological form of disease onset. They predominantly manifested with early-onset visceral manifestations in the form of hepatosplenomegaly and prolonged neonatal jaundice, and late-onset neuropsychiatric manifestations in the form of vertical supranuclear gaze palsy (VSGP), ataxia, cognitive impairment and seizures. Brain MRI in 6 patients was normal in 5 or consistent with cerebellar hemisphere atrophy in 1 of them. Two other mutations were identified in the NPC1 gene, of which p.V845Cfs*24 was novel.ConclusionsOur results revealed phenotypic heterogeneity of NPC even within the same genotype, and add to the increasingly recognized evidence that cholestatic jaundice and hepatosplenomegaly during infancy, should alert the physician for the possibility of NPC. We reported a novel mutation in the NPC1 gene further expanding its genotype.
Highlights
Niemann–Pick disease type C (NPC) is an autosomal recessive, neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes
The majority of patients were referred for evaluation because they had features suggestive of a non-specific neurometabolic disorder, especially in the context of a previously affected family member, while the others were referred in the early infantile period because of a previous confirmed diagnosis of NPC in one of the family members
We reported sixteen patients (9 females and 7 males) of NPC disease aged from 1 month to 30 years belonging to 9 families
Summary
Niemann–Pick disease type C (NPC) is an autosomal recessive, neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. Mutations in these genes are associated with abnormal endosomal–lysosomal trafficking, resulting in the accumulation of tissue-specific lipids in lysosomes. Niemann–Pick disease type c (NPC) disease is a rare, pan-ethnic autosomal recessive, neurovisceral lysosomal storage disease with an incidence of 1 in 100,000– 120,000 live births. Patient no Gender, ID and age Consanguinity. Age of onset and clinical outcome Brain MRI F, AAa 8 years F, JAa 4 years M, MMe 20 years
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