Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients

Hollak, Carla E. M.; Sonnaville, E S de; Cassiman, David; Linthorst, Gabor E.; Groener, J.E.M.; Morava, Éva; Wevers, Ron A.; Mannens, Marcel M.A.M.; Aerts, Johannes M. F. G.; Meersseman, Wouter; Akkerman, Erik M.; Niezen-Koning, Klary E.; Mulder, Margot F.; Visser, Gerard H.A.; Wijburg, Frits A.; Lefeber, Dirk; Poorthuis, Ben J. H. M.

doi:10.1016/j.ymgme.2012.06.015

Cited by 77 publications

(107 citation statements)

References 25 publications

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“…Death classically occurs between 1.5 and 3 years of life (McGovern et al 2006). By contrast, typical type B NPD (MIM# 607616) is a chronic, non-neuronopathic form, with a widely variable degree of systemic involvement (McGovern et al 2008;Hollak et al 2012). The most typical symptoms are hepatosplenomegaly, interstitial lung disease, alteration of liver function, followed by joint/limb pain, bruising, headache, abdominal pain or diarrhoea.…”

Section: Introductionmentioning

confidence: 99%

Cirrhosis and Liver Failure: Expanding Phenotype of Acid Sphingomyelinase-Deficient Niemann-Pick Disease in Adulthood

et al. 2014

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Section: Introductionmentioning

confidence: 99%

Cirrhosis and Liver Failure: Expanding Phenotype of Acid Sphingomyelinase-Deficient Niemann-Pick Disease in Adulthood

et al. 2014

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“…31 La hepatoesplenomegalia fue un dato constante y progresivo en nuestra serie, 100% con elevación de transaminasas y bilirrubinas, generando en algunos un incremento de la sintomatología respiratoria por un tórax restrictivo. Uno de los 3 pacientes con ascitis presentó falla hepática que condicionó su muerte en pocas semanas.…”

Section: Discussionunclassified

Enfermedad de Niemann Pick tipo-A. Presentación de 12 casos

2017

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ResumenINTRODUCCIÓN: la enfermedad de Niemann Pick tipo A es una enfermedad hereditaria de depósito lisosomal, debida a un déficit de la enzima esfingomielinasa ácida, lo que da lugar a la acumulación de esfingomielina en las células del sistema reticuloendotelial y nervioso central.OBJETIVO: se describe el curso de la enfermedad de Niemann Pick tipo A en 12 pacientes: tres niños y nueve niñas, con edades entre 3 a 33 meses. MATERIAL Y MÉTODOS:estudio retrospectivo efectuado con base en la información de los expedientes de 12 pacientes, evaluados mediante un examen físico completo, oftalmológico, análisis de laboratorio, ultrasonido de abdomen, tomografía axial computarizada o resonancia magnética nuclear cerebral, radiografías de tórax, ecocardiograma, electroencefalograma, potenciales evocados auditivos y visuales, serie esofagogastroduodenal y serie ósea. Se obtuvo información sobre enfermedades intercurrentes y causas de muerte.RESULTADOS: la sintomatología comenzó en promedio a los 5.9 meses (2 a 16 meses) y el diagnóstico definitivo se realizó a la edad de los 15.6 meses (3 a 33 meses) a través del cuadro clínico sugestivo, con presencia de células espumosas en el aspirado de médula ósea 12/12 (100%) y deficiencia de la enzima esfingomielinasa ácida en 12/12 pacientes (100%); la biopsia hepática fue sugestiva de enfermedad por atesoramiento en 5/12 (41.6%). Las manifestaciones clínicas por orden de frecuencia fueron: hepatoesplenomegalia y afección neurológica en 12/12 (100%), alteración pulmonar 11/12 (91.6%), hematológica 9/12 (80%), oftalmológica con mancha rojo cereza 9/12 (75%), ósea 6/12 (50%), y cardiaca 4/12 (33.3%). Únicamente hubo antecedente de consanguinidad en 4 familias (33.3%).CONCLUSIONES: el curso clínico de la enfermedad de Niemann Pick tipo A es muy similar entre los pacientes afectados, el primer dato clínico detectado es la hepatoesplenomegalia. Los pacientes están asintomáticos los primeros 4 meses de vida, posterior a los cuales presentan un curso neurodegenerativo que conduce a la muerte antes de los 3 años. PALABRAS CLAVE: enfermedad de

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“…In contrast, type B patients have no overt signs of CNS involvement, but hepatosplenomegaly may be profound and accompanied by signs of liver failure [16][17][18]. Serum triglycerides and LDL-cholesterol are often elevated, while HDL-cholesterol is low.…”

Section: Clinical Features and Diagnostic Evaluationmentioning

confidence: 99%

“…Organomegaly can be significant, with an average splenic volume greater than ten multiples of normal [16][17][18]. Children with type B NPD often have growth restriction, particularly of linear growth, which is associated with a delayed bone age.…”

Section: Natural Historymentioning

confidence: 99%

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Types A and B Niemann–Pick Disease

Wasserstein

and

Schuchman

2012

Lysosomal Storage Disorders

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The eponym Niemann-Pick disease (NPD) refers to a group of patients who present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features including hepatosplenomegaly, pulmonary insufficiency and/or central nervous system (CNS) involvement. Due to the pioneering work of Roscoe Brady and co-workers, we now know that there are two distinct metabolic abnormalities that account for NPD. The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM; "types A & B" NPD), and the second is due to defective function in cholesterol transport ("type C" NPD). Herein only types A and B NPD will be discussed. Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement. They rarely survive beyond 2-3 years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Intermediate patients also have been reported with mild to moderate neurological findings. All patients with types A and B NPD have mutations in the gene encoding ASM (SMPD1), and thus the disease is more accurately referred to as ASM deficiency (ASMD). Herein we will review the clinical, pathological, biochemical, and genetic findings in types A and B NPD, and emphasize the seminal contributions of Dr. Brady to this disease. We will also discuss the current status of therapy for this disorder.

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Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients

Cited by 77 publications

References 25 publications

Cirrhosis and Liver Failure: Expanding Phenotype of Acid Sphingomyelinase-Deficient Niemann-Pick Disease in Adulthood

Cirrhosis and Liver Failure: Expanding Phenotype of Acid Sphingomyelinase-Deficient Niemann-Pick Disease in Adulthood

Enfermedad de Niemann Pick tipo-A. Presentación de 12 casos

Types A and B Niemann–Pick Disease

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