A novel mutation in SMPD1 gene in a patient with Niemman-Pick disease

Introduction: Niemman-Pick disease type A (NMP-A) is a congenital inherited disease, which is caused by deficiency in acid sphingomyelinase of lysosomes. Accumulation of sphingomyelin in lysosomes leads to cellular apoptosis and as a consequence hepatosplenomegaly, neurodegenerative disorder and failure to thrive occur. A cherry red spot of the macula and the foamy cells in bone marrow are the other manifestations of the disease that help with diagnosis. Three main types of the disease that has been classified are: type A, B and C. Type A is a rare untreatable disease due to a mutation in the SMPD1 gene with early manifestations and poor prognosis.Materials & Methods: This article is a case report of a new mutation in a patient of our clinic ,who suffers from Niemman-Pick disease, a rare metabolic disorderResults: Case presentation: A one year old boy was referred to the pediatric outpatient clinic due to abdominal distention and poor weight gain. He was the first boy of his consanguineous parents. Other findings of history and physical examination were neurodevelopmental delay, hepatosplenomegaly, severe hypotonia, difficulty in breathing, and a little coarse face with open mouth and protruded tongue. At first he was diagnosed as muccopolysacharidosis (MPS) clinically, because of rough facial features, but further work up ruled out MPS. Ophthalmological examination showed cherry red spots in his macula. So enzyme study was done and the level of acid sphingomyelinase was less than normal. Homozygous variant as c.682T> G in exon 2 of the SMPD1 gene (NM_000543) was detected that was classified as a variant of unknown significance. More evaluation of his parents with Sanger sequencing showed a heterozygous variant of c.682T> G in exon 2 of the SMPD1 gene in both of them.Conclusion & discussion: This variant of the SMPD1 gene can be defined as pathogenic. Furthermore, it seems that mild coarse facial features can be seen in Niemann-Pick type A

کلیدواژه ها:

Niemman-Pick disease type A ، Acid sphingomyelinase ، Whole Exome Sequencing ، Hypotonia