ABSTRACT
INTRODUCTION AND OBJECTIVES: Niemann-Pick disease type A (NPD-A) and B (NPD-B) are lysosomal storage diseases with a birth prevalence of 0.4-0.6/100,000. They are caused by a deficiency in acid sphingomyelinase, an enzyme encoded by SMPD1. We analyzed the phenotype and genotype of four unrelated Mexican patients, one with NPD-A and three with NPD-B. PATIENTS AND METHODS: Four female patients between 1 and 7 years of age were diagnosed with NPD-A or NPD-B by hepatosplenomegaly, among other clinical characteristics, and by determining the level of acid sphingomyelinase enzymatic activity and sequencing of the SMPD1 gene. Additionally, a 775bp amplicon of SMPD1 (from 11:6393835_6394609, including exons 5 and 6) was analyzed by capillary sequencing in a control group of 50 unrelated healthy Mexican Mestizos. RESULTS: An infrequent variant (c.1343A>G p.Tyr448Cys) was observed in two patients. One is the first NPD-A homozygous patient reported with this variant and the other a compound heterozygous NPD-B patient with the c.1829_1831delGCC p.Arg610del variant. Another compound heterozygous patient had the c.1547A>G p.His516Arg variant (not previously described in affected individuals) along with the c.1805G>A p.Arg602His variant. A new c.1263+8C>T pathogenic variant was encountered in a homozygous state in a NPD-B patient. Among the healthy control individuals there was a heterozygous carrier for the c.1550A>T (rs142787001) pathogenic variant, but none with the known pathogenic variants in the 11:6393835_6394609 region of SMPD1. CONCLUSIONS: The present study provides further NPD-A or B phenotype-genotype correlations. We detected a heterozygous carrier with a pathogenic variant in 1/50 healthy Mexican mestizos.
Subject(s)
Niemann-Pick Disease, Type A/genetics , Niemann-Pick Disease, Type B/genetics , Sphingomyelin Phosphodiesterase/genetics , Adolescent , Adult , Child , Child, Preschool , Epistaxis/physiopathology , Female , Genetic Carrier Screening , Genotype , Growth Disorders/physiopathology , Healthy Volunteers , Hepatomegaly/physiopathology , Heterozygote , Humans , Infant , Liver/pathology , Liver/ultrastructure , Mexico , Niemann-Pick Disease, Type A/metabolism , Niemann-Pick Disease, Type A/pathology , Niemann-Pick Disease, Type A/physiopathology , Niemann-Pick Disease, Type B/metabolism , Niemann-Pick Disease, Type B/pathology , Niemann-Pick Disease, Type B/physiopathology , Phenotype , Sphingomyelin Phosphodiesterase/metabolism , Splenomegaly/physiopathology , Young AdultABSTRACT
BACKGROUND: Gaucher disease type 1 (GD1, OMIM# 230800), is a condition with high impact in patient's quality of life (QoL). We report the improvement in QoL of children with GD1 measured by Lansky play-performance scale (LS) after enzymatic replacement therapy (ERT) and to describe our experience in the treatment of children with GD1. METHODS: Five children with diagnosis of GD1 received imiglucerase 60 mg/kg every two weeks. LS, hepatomegaly, splenomegaly, hemoglobin, platelets, and growth rate were measured every 6 months after beginning ERT for 30 months. RESULTS: After ERT, LS increased significantly from 28 ± 16.48 points before ERT to 70 ± 10 (P = 0.0046) and 95 ± 10 (P = 0.0022) points after 6 and 30 months of ERT, respectively; hemoglobin and platelets changed significantly from 9.28 ± 0.61 to 12.40 ± 0.85 (P = 0.0198) and from 71.50 ± 14.89 to 205.00 ± 65.34 (P = 0.0428) after 30 months of ERT, respectively. All patients demonstrated decreased hepatic and splenic size with mean reductions of 66% and 80% at 30 months of treatment and the USG longitudinal axis was reduced in both liver and spleen after ERT. CONCLUSION: The use of ERT with imiglucerase 60 mg/kg every two weeks has substantial benefits and significantly improves QoL, assessed with Lansky Score, of the five children with GD1 studied.
