TY - JOUR
T1 - Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium
T2 - Disease spectrum and natural course in attenuated patients
AU - Hollak, C. E.M.
AU - de Sonnaville, E. S.V.
AU - Cassiman, D.
AU - Linthorst, G. E.
AU - Groener, J. E.
AU - Morava, E.
AU - Wevers, R. A.
AU - Mannens, M.
AU - Aerts, J. M.F.G.
AU - Meersseman, W.
AU - Akkerman, E.
AU - Niezen-Koning, K. E.
AU - Mulder, M. F.
AU - Visser, G.
AU - Wijburg, F. A.
AU - Lefeber, D.
AU - Poorthuis, B. J.H.M.
N1 - Funding Information:
We acknowledge the Niemann–Pick patients and their families who have participated in this study and Annick van Clooster for her assistance. This work was supported by the Dutch Top Institute Pharma project nr. [ T6-208 ]: Sustainable Orphan Drug Development through Registries and Monitoring.
PY - 2012/11
Y1 - 2012/11
N2 - Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients.Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12. months for pulmonary function tests, 6. minute walk test (6MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers.Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13. years, range 1-59. years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60. years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11. years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6. years, with some decline in pulmonary function and 6MWT. Bone marrow fat fractions were decreased, indicating the presence of storage macrophages. Lung involvement was not related to the extent of visceromegaly, cytopenia or bone marrow involvement.In conclusion, in NPD-B patients pulmonary disease is the most debilitating feature. Disease manifestations are mostly stable in attenuated patients. Bone marrow infiltration is a less prominent feature of the disease.
AB - Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients.Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12. months for pulmonary function tests, 6. minute walk test (6MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers.Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13. years, range 1-59. years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60. years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11. years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6. years, with some decline in pulmonary function and 6MWT. Bone marrow fat fractions were decreased, indicating the presence of storage macrophages. Lung involvement was not related to the extent of visceromegaly, cytopenia or bone marrow involvement.In conclusion, in NPD-B patients pulmonary disease is the most debilitating feature. Disease manifestations are mostly stable in attenuated patients. Bone marrow infiltration is a less prominent feature of the disease.
KW - Acid sphingomyelinase (ASM) deficiency
KW - Chitotriosidase
KW - Enzyme replacement therapy
KW - Niemann-Pick disease type B
KW - Pulmonary disease
KW - Quantitative chemical shift imaging
UR - http://www.scopus.com/inward/record.url?scp=84867897494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867897494&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2012.06.015
DO - 10.1016/j.ymgme.2012.06.015
M3 - Article
C2 - 22818240
AN - SCOPUS:84867897494
SN - 1096-7192
VL - 107
SP - 526
EP - 533
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 3
ER -