Clinical and Genetic Characteristics of Mexican Patients with Juvenile Presentation of Niemann-Pick Type C Disease

الملخص EN

Niemann-Pick type C disease (NPC) is a rare lysosomal disease with a protean presentation, ranging from a fatal neonatal course with visceromegaly to an adult presentation with only neurological or psychiatric symptomatology.

In this report we describe the genetic and clinical characteristics of 3 Mexican patients from different families with juvenile presentation of NPC.

Clinical examination, imaging of central nervous and gastrointestinal system, and EEG were performed.

Genetic studies include sequencing and deletion/duplication analysis of NPC1 and NPC2 genes.

All patients presented with cognitive impairment, ataxia, and supranuclear vertical gaze palsy; one case had gelastic cataplexy.

Also they developed epilepsy and cortical atrophy and two patients had thinning of corpus callosum.

The 3 patients were compound heterozygotes for NPC1 sequence variants, including 5 missense and 1 nonsense mutations: p.P1007A and p.F1087L in Case 1; p.Q921P and p.G992R in Case 2; and p.R348* and p.V1165M in case 3.

Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity.

This suggests a relative high frequency of mutation carriers as it is reported for European population.

Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.