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Clinical, biochemical, and genotype‐phenotype correlations of 118 patients with Niemann‐Pick disease Types A/B
Author(s) -
Hu Jiayue,
Maegawa Gustavo H.B.,
Zhan Xia,
Gao Xiaolan,
Wang Yu,
Xu Feng,
Qiu Wenjuan,
Han Lianshu,
Gu Xuefan,
Zhang Huiwen
Publication year - 2021
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24192
Subject(s) - acid sphingomyelinase , biology , genotype , phenotype , niemann–pick disease , allele , disease , clinical phenotype , age of onset , medicine , sphingomyelin phosphodiesterase , genetics , gene , sphingomyelin , gastroenterology , endocrinology , cholesterol
Niemann‐Pick disease Types A and B (NPA/B) are autosomal recessive disorders caused by variants in the sphingomyelin phosphodiesterase‐1 ( SMPD1 ) gene. This study aimed to describe and characterize a cohort of 118 patients diagnosed with NPA/B based on clinical, biochemical, and molecular findings, and to identify sound correlations between laboratory findings and clinical presentations. Decreased peripheral leukocyte acid sphingomyelinase activity levels and increased plasma 7‐ketocholesterol levels were significantly correlated with disease onset and severity of the clinical course. We identified 92 different sequence SMPD1 variants, including 41 novel variants, in 118 NPA/B patients (19 NPA, 24 intermediate type, 75 NPB). The most prevalent mutation was p.Arg602His, which accounted for 9.3% of the alleles. Patients homozygous for p.Arg602His or p.Asn522Ser showed a late‐onset form of the NPB phenotype. The homozygous SMPD1 variant p.Tyr500His correlated with the early‐onset NPB clinical form. Additionally, homozygous variants p.His284SerfsX18, p.Phe465Ser, and p.Ser486Arg were associated with the neuronopathic NPA clinical form. The homozygous variant p.Arg3AlafsX74 was associated with the intermediate clinical form. Our study contributes to the understanding of the natural history of NPA/B and assists in the development of efficacious treatments for patients afflicted with this devastating lysosomal storage disorder.