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

C. E.M. Hollak, E. S.V. de Sonnaville, D. Cassiman, G. E. Linthorst, J. E. Groener, Eva Morava-Kozicz, R. A. Wevers, M. Mannens, J. M.F.G. Aerts, W. Meersseman, E. Akkerman, K. E. Niezen-Koning, M. F. Mulder, G. Visser, F. A. Wijburg, D. Lefeber, B. J.H.M. Poorthuis

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)526-533
Number of pages8
JournalMolecular Genetics and Metabolism
Volume107
Issue number3
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

Fingerprint

Type A Niemann-Pick Disease
Sphingomyelin Phosphodiesterase
Belgium
Netherlands
Niemann-Pick Diseases
Acids
Bone
Bone Marrow
Pulmonary diseases
Infiltration
Lung
Lung Diseases
Type B Niemann-Pick Disease
Enzyme Replacement Therapy

Keywords

  • Acid sphingomyelinase (ASM) deficiency
  • Chitotriosidase
  • Enzyme replacement therapy
  • Niemann-Pick disease type B
  • Pulmonary disease
  • Quantitative chemical shift imaging

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium : Disease spectrum and natural course in attenuated patients. / Hollak, C. E.M.; de Sonnaville, E. S.V.; Cassiman, D.; Linthorst, G. E.; Groener, J. E.; Morava-Kozicz, Eva; Wevers, R. A.; Mannens, M.; Aerts, J. M.F.G.; Meersseman, W.; Akkerman, E.; Niezen-Koning, K. E.; Mulder, M. F.; Visser, G.; Wijburg, F. A.; Lefeber, D.; Poorthuis, B. J.H.M.

In: Molecular Genetics and Metabolism, Vol. 107, No. 3, 01.11.2012, p. 526-533.

Research output: Contribution to journalArticle

Hollak, CEM, de Sonnaville, ESV, Cassiman, D, Linthorst, GE, Groener, JE, Morava-Kozicz, E, Wevers, RA, Mannens, M, Aerts, JMFG, Meersseman, W, Akkerman, E, Niezen-Koning, KE, Mulder, MF, Visser, G, Wijburg, FA, Lefeber, D & Poorthuis, BJHM 2012, 'Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients', Molecular Genetics and Metabolism, vol. 107, no. 3, pp. 526-533. https://doi.org/10.1016/j.ymgme.2012.06.015
Hollak, C. E.M. ; de Sonnaville, E. S.V. ; Cassiman, D. ; Linthorst, G. E. ; Groener, J. E. ; Morava-Kozicz, Eva ; Wevers, R. A. ; Mannens, M. ; Aerts, J. M.F.G. ; Meersseman, W. ; Akkerman, E. ; Niezen-Koning, K. E. ; Mulder, M. F. ; Visser, G. ; Wijburg, F. A. ; Lefeber, D. ; Poorthuis, B. J.H.M. / Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium : Disease spectrum and natural course in attenuated patients. In: Molecular Genetics and Metabolism. 2012 ; Vol. 107, No. 3. pp. 526-533.
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abstract = "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.",
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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-Kozicz, Eva

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.

PY - 2012/11/1

Y1 - 2012/11/1

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

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