RESUMO
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.
Assuntos
Doença de Niemann-Pick Tipo A/genética , Doença de Niemann-Pick Tipo B/genética , Esfingomielina Fosfodiesterase/genética , Adolescente , Adulto , Criança , Pré-Escolar , Epistaxe/fisiopatologia , Feminino , Triagem de Portadores Genéticos , Genótipo , Transtornos do Crescimento/fisiopatologia , Voluntários Saudáveis , Hepatomegalia/fisiopatologia , Heterozigoto , Humanos , Lactente , Fígado/patologia , Fígado/ultraestrutura , México , Doença de Niemann-Pick Tipo A/metabolismo , Doença de Niemann-Pick Tipo A/patologia , Doença de Niemann-Pick Tipo A/fisiopatologia , Doença de Niemann-Pick Tipo B/metabolismo , Doença de Niemann-Pick Tipo B/patologia , Doença de Niemann-Pick Tipo B/fisiopatologia , Fenótipo , Esfingomielina Fosfodiesterase/metabolismo , Esplenomegalia/fisiopatologia , Adulto JovemRESUMO
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 16-year-old Mexican mestizo woman with a NPD type B phenotype who presented hepatosplenomegaly, persitstenly 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 n which foamy histiocytes were noticed and diagnosis of NiemannPick disease was suspected; and confirmed by biochemical and molecular tests. The missense c.1343 A>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.1343 A>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.
Assuntos
Doença de Niemann-Pick Tipo B/genética , Esfingomielina Fosfodiesterase/genética , Adulto , Feminino , Humanos , México , Doença de Niemann-Pick Tipo B/metabolismo , Doença de Niemann-Pick Tipo B/patologia , Adulto JovemRESUMO
Generalized lichen nitidus is an uncommon chronic inflammatory dermatosis with very characteristic histological findings. Its pathogenesis is still unclear; very rarely it has been associated with genetic disorders. Herein we report the case of a 12-year-old boy with Niemann-Pick disease who developed generalized lichen nitidus.
Líquen nítido generalizado é uma dermatose inflamatória crônica, rara, com achados histológicos muito característicos. Sua patogênese não está completamente esclarecida e, muito raramente, tem sido associado a doenças genéticas. Reportamos o caso de um doente do sexo masculino, de 12 anos de idade, com Doença de Niemann-Pick, que desenvolveu líquen nítido generalizado.
Assuntos
Criança , Humanos , Masculino , Líquen Nítido/genética , Doença de Niemann-Pick Tipo B/complicações , Doença Crônica , Líquen Nítido/patologia , Doença de Niemann-Pick Tipo B/patologia , Pele/patologiaRESUMO
Generalized lichen nitidus is an uncommon chronic inflammatory dermatosis with very characteristic histological findings. Its pathogenesis is still unclear; very rarely it has been associated with genetic disorders. Herein we report the case of a 12-year-old boy with Niemann-Pick disease who developed generalized lichen nitidus.
Assuntos
Líquen Nítido/genética , Doença de Niemann-Pick Tipo B/complicações , Criança , Doença Crônica , Humanos , Líquen Nítido/patologia , Masculino , Doença de Niemann-Pick Tipo B/patologia , Pele/patologiaRESUMO
Niemann-Pick disease is a rare inherited autosomal recessive disorder, currently classified into six subtypes and characterized by the intracellular accumulation of sphingomyelin in the liver, spleen, lungs, bone marrow or brain. The main pulmonary abnormalities described in high-resolution computed tomography (HRCT) of the chest consist of thickening of the interlobular septa and ground-glass opacities. This case report describes a patient with subtype B Niemann-Pick disease characterized by cysts and ground-glass opacities that were detected on HRCT of the chest.