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Clinical, biomarker and genetic spectrum of Niemann-Pick type C in Egypt

Iman G. Mahmoud 1 et al.
1 Cairo University
January 11, 2019

Clin Genet. 2019 Jan 11. doi: 10.1111/cge.13492. [Epub ahead of print]

Abstract

Niemann-Pick type C (NPC) is an autosomal recessive condition which is caused by bi-allelic variants in either NPC1 (95% of patients) or NPC2 (5%). It manifests with mainly neurological symptoms. Sphingomyelin Lyso-SM-509 has recently been proposed as a potential NPC biomarker.

We recruited a cohort of 23 unrelated patients who had received a clinical diagnosis of NPC. Genetic analysis identified bi-allelic variants in NPC1 in all of them. Twenty patients were homozygous, while three were compound heterozygous. Nine of the variants were novel. Detailed clinical workup enabled stratification of the patients into four distinct groups. Dried blood spots for mass spectrometry-based determination of Lyso-SM-509 were available for 20 patients. Concentrations were elevated in all cases, suggesting high sensitivity of this biomarker for NPC.

In summary, we present the first analysis of a large cohort of Egyptian NPC patients. Our findings add valuable novel insights into the mutational and clinical spectra associated with this rare disease. We furthermore corroborate high diagnostic value of Lyso-SM-509 as measured from dried blood spots. Further studies that aim at systematically defining diagnostic performance of this biomarker are warranted.