Lysomal Storage Disorder

The Octopus

ASMD

ASMD (= Acid Sphingomyelinase Deficiency, Niemann-Pick Disease Type A/B) is based on the deficiency of the enzyme acid sphingomyelinase, which is caused by a defect in the SMPD1 gene. The lack of acid sphingomelinase leads to an accumulation of sphingomyelin in the cells of various organs (e.g. spleen and liver). Three clinical phenotypes are distinguished: infantile neurovisceral ASMD (Niemann-Pick disease type A), chronic neurovisceral ASMD (Niemann-Pick disease type A/B) and chronic visceral ASMD (Niemann-Pick disease type B). Infantile neurovisceral ASMD is characterized by hepatosplenomegaly, failure to thrive, psychomotor developmental retardation and progressive neurodegeneration. Life expectancy is significantly limited. Clinical signs of chronic neurovisceral ASMD include hepatosplenomegaly, interstitial lung disease and variable neurological symptoms (including ataxia, peripheral neuropathy, cognitive impairment). Visceral symptoms, such as hepatosplenomegaly and interstitial lung disease, are typical for chronic visceral ASMD. Enzyme replacement therapy with recombinant acid sphingomyelinase is currently in clinical trials.

ASMD | SphinCS - Clinical Science for LSD

Synonym: Niemann-Pick Disease Type A/B
Etiology: Deficiency of acid sphingomyelinase 
Gene: SMPD1 Gene
Mode of inheritance: Autosomal recessive

Phenotypes:

  • Infantile neuroviscerale ASMD (Niemann-Pick Disease Type A)
  • Chronic neuroviscerale ASMD (Niemann-Pick Disease Typ A/B)
  • Chronic viscerale ASMD (Niemann-Pick Disease Type B)

Leading symptoms:

Infantile neuroviszerale ASMD
(Age of onset: infancy)

  • Hepatosplenomegaly
  • Recurrent airway infections
  • Muscular hypotonia
  • Psychomotor development delay/ regression
  • Progressive neurodegeneration
  • Failure to thrive
  • Cherry red spot
  • Cytopenia (thrombocytopenia, leukopenia)

Chronic neuroviscerale ASMD
(Age of onset: childhood)

  • Hepatosplenomegaly
  • Interstitial lung disease
  • Dyslipidemia
  • Cytopenia (thrombocytopenia, leucopenia)
  • Cognitive impairment
  • Ataxia
  • Peripheral neuropathy
  • Heart valve disease, arteriosclerosis

Chronic viscerale ASMD
(Age of onset: childhood, adolescence)

  • Hepatosplenomegaly
  • Interstitial lung disease
  • Dyslipidemia
  • Cytopenia (thrombocytopenia, leucopenia)
  • Heart valve disease, arteriosclerosis

Diagnostics:

  • Measurement of the activity of acid sphingomyelinase in leucocytes or dried blood spot
  • Lyso-Sphingomyelin
  • Molecular genetic analysis of SMPD1 Gene

Therapy:
Only symptomatic

Current Studies

ASMD
LTS13632
A long-term study to assess the ongoing safety and efficacy of olipudase alfa in
patients with acid sphingomyelinase deficiency
Age

No information
(participation in previous study required)

Status active

Patient admission closed

Institution SphinCS GmbH

Drug trial
ASMD
PIR 16813
A prospective and retrospective cohort study to refine and expand the knowledge on patients with chronic forms of ASMD
Age

No age limit

Status active

Patient admission recruiting

Institution SphinCS GmbH

Natural-History-Study
ASMD M. Niemann-Pick Typ C
INPDR-NP registry
International Niemann-Pick Disease Registry – An International Rare Disease Registry for
Niemann-Pick Disease Type A, B or C.
Age

No age limit

Status active

Patient admission recruiting

Institution SphinCS Lyso gemeinnützige UG (haftungsbeschränkt)

Register-Study
The "U.S. National Library of Medicine" provides a complete list of all international studies at www.clinicaltrials.gov. The comparable EU website is less comprehensive: www.clinicaltrialsregister.eu.

Self-help groups

At the moment we are not aware of any self-help groups.

Literature

Cassiman, D., S. Packman, B. Bembi, H. B. Turkia, M. Al-Sayed, M. Schiff, J. Imrie, P. Mabe, T. Takahashi, K. E. Mengel, R. Giugliani, and G. F. Cox.

Cause of Death in PaLents with Chronic Visceral and Chronic Neurovisceral Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B and B Variant): Literature Review and Report of New Cases

Cassiman, D., S. Packman, B. Bembi, H. B. Turkia, M. Al-Sayed, M. Schiff, J. Imrie, P. Mabe, T. Takahashi, K. E. Mengel, R. Giugliani, and G. F. Cox.

Corrigendum to "Cause of Death in PaLents with Chronic Visceral and Chronic Neurovisceral Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B and B Variant): Literature Review and Report of New Cases

Harzer, K., A. Rolfs, P. Bauer, M. Zschiesche, E. Mengel, J. Backes, B. Kustermann-Kuhn, G. Bruchelt, O. P. van Diggelen, H. Mayrhofer, and I. Krageloh-Mann. 

Niemann-Pick Disease Type a and B Are Clinically but Also EnzymaLcally Heterogeneous: Pihall in the Laboratory Diagnosis of Sphingomyelinase Deficiency Associated with the MutaLon Q292 K.

McGovern, M. M., C. Dionisi-Vici, R. Giugliani, P. Hwu, O. Lidove, Z. Lukacs, K. Eugen Mengel, P. K. Mistry, E. H. Schuchman, and M. P. Wasserstein. 

Consensus RecommendaLon for a DiagnosLc Guideline for Acid Sphingomyelinase Deficiency

McGovern, M. M., M. P. Wasserstein, R. Giugliani, B. Bembi, M. T. Vanier, E. Mengel, S. E. Brodie, D. Mendelson, G. Skloot, R. J. Desnick, N. Kuriyama, and G. F. Cox. 

A ProspecLve, Cross- SecLonal Survey Study of the Natural History of Niemann-Pick Disease Type B

Mendelson, D. S., M. P. Wasserstein, R. J. Desnick, R. Glass, W. Simpson, G. Skloot, M. Vanier, B. Bembi, R. Giugliani, E. Mengel, G. F. Cox, and M. M. McGovern. 

Type B Niemann-Pick Disease: Findings at Chest Radiography, Thin-SecLon Ct, and Pulmonary FuncLon TesLng.

Ries, M., E. Schaefer, T. Luhrs, L. Mani, J. Kuhn, M. T. Vanier, F. Krummenauer, A. Gal, M. Beck, and E. Mengel

CriLcal Assessment of Chitotriosidase Analysis in the RaLonal Laboratory Diagnosis of Children with Gaucher Disease and Niemann-Pick Disease Type a/B and C

Valayannopoulos, V., E. Mengel, A. Brassier, and G. Grabowski.

Lysosomal Acid Lipase Deficiency: Expanding DifferenLal Diagnosis

Van Diggelen, O. P., Y. V. Voznyi, J. L. Keulemans, K. Schoonderwoerd, J. Ledvinova, E. Mengel, M. Zschiesche, R. Santer, and K. Harzer. 

A New Fluorimetric Enzyme Assay for the Diagnosis of Niemann-Pick a/B, with Specificity of Natural Sphingomyelinase Substrate

Vom Dahl, S., and E. Mengel

Lysosomal Storage Diseases as DifferenLal Diagnosis of Hepatosplenomegaly

Wasserstein, M., C. Dionisi-Vici, R. Giugliani, W. L. Hwu, O. Lidove, Z. Lukacs, E. Mengel, P. K. Mistry, E. H. Schuchman, and M. McGovern.

Recommendations for Clinical Monitoring of PaLents with Acid Sphingomyelinase Deficiency (Asmd)

At present we have no literature available.