Rabbit Anti Human SMPD1 (C-term) polyclonal antibody

Pathogenic compound heterozygous mutations in a Mexican mestizo patient with Niemann-Pick disease type B: Niemann-Pick disease (NPD) type B is a lysosomal storage disorder caused by a deficiency of acid sphingomyelinase (ASM). We report the clinical follow-up of a 19-year-old Mexican mestizo woman with a NPD type B phenotype who presented hepatosplenomegaly, persistently low high-density lipoprotein (HDL) cholesterol and thrombocytopenia, without central nervous system involvement. After of a dengue fever episode with severe anemia and pancytopenia, leading to a bone marrow study in which foamy histiocytes were noticed and diagnosis of Niemann Pick disease was suspected; and confirmed by biochemical and molecular tests. The missense c.1343A>G (p.Tyr448Cys, formerly Y446C) and c.1426C>T (p.Arg476Trp, formerly R474W) mutations in the SMPD1 gene were identified. These mutations have never been reported in the Mexican population. Since the c.1343A>G (Y446C) mutation has been previously reported in a Japanese patient with NPD type A, we suggest an attenuator effect of c.1426C>T (R474W) allele (previously associated with the NPD type B phenotype). In conclusion, this is the first description of the concomitant occurrence of Y446C and R476W mutations in a Mexican patient with NPD type B, showing the importance of increased awareness and availability of specialized diagnostic tests in the diagnosis of rare inherited metabolic diseases.

Niemann Pick type C (NP-C) is a rare neurodegenerative disorder caused by an impairment of intracellular lipid transport. Due to the heterogeneous clinical phenotype and the lack of a reliable blood test, diagnosis and therapy are often delayed for years. In the cell, accumulating cholesterol leads to increased formation of oxysterols that can be used as a powerful screening parameter for NP-C. In a large scale study, we evaluated the oxysterol cholestane-3 beta, 5a, 6 beta-triol (c-triol) as potential biomarker for a rapid diagnosis of NP-C. Using GC/MS, c-triol has been analyzed in 1902 plasma samples of patients with the suspicion for NP-C. Diagnosis in patients with elevated oxysterols was confirmed by genetic analysis. 71 new NP-C patients (69 NP-C1 and two NP-C2) and 12 Niemann Pick type A/B patients were identified. 24 new mutations in NPC1, one new mutation in NPC2 and three new mutations in the SMPD1 gene were found. Cholestane-3 beta, 5 alpha, 6 alpha-triol was elevated in Niemann Pick type C1, type C2, type A/B and in CESD disease. No other study has ever identified so many NP-C patients, proving that c-triol is a rapid and reliable biomarker to detect patients with NP-C disease and related cholesterol transport disorders. It should replace the filipin test as the first-line diagnostic assay. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).