Lysomal Storage Disorder

The Chameleon

M. Niemann-Pick Typ C

In Niemann-Pick disease type C, a defect in the NPC1 gene (approximately 95% of cases) or in the NPC2 gene (approx. 5% of cases) leads to impaired intracellular cholesterol trafficking and consecutive to accumulation of unesterified cholesterol in the cells of various organs. The age of manifestation extends from the perinatal period to late adulthood. Clinical symptoms are very heterogeneous. In addition to visceral signs – consisting of a splenomegaly or hepatosplenomegaly – neurological symptoms, such as progressive cerebellar ataxia, dysarthria, vertical supranuclear gaze palsy, epilepsy, cataplexy and progressive dementia are characteristic. For the treatment of progressive neurological symptoms, substrate reduction therapy with miglustat is currently available.

M. Niemann-Pick Typ C | SphinCS - Clinical Science for LSD

Synonym: Disordered intracellular lipid transport
Gene: NPC1 Gene; NPC2 Gene
Mode of inheritance: Autosomal recessive
Phenotypes:

  • Pre-/perinatal 
  • Early-infantile
  • Late-infantile
  • Juvenile
  • Adult 

Leading symptoms:

Pre-/perinatal
(Age of onset: < 2 months)

  • Fetal ascites/ Hydrops fetalis
  • Hepatosplenomegaly
  • Cholestatic Hepatopathy (Icterus prolongatus)
  • Muscular hypotonia
  • Pulmonale manifestation (NPC2)

Early-infantile
(Age of onset: 2 months to 1 year)

  • Hepatosplenomegaly or isolated splenomegaly
  • Psychomotor development delay/arrest
  • Spasticity
  • Vertical supranuclear gaze palsy

Late-infantile
(Age of onset: 2 months to 1 year)

  • Hepatosplenomegaly or isolated splenomegaly
  • Psychomotor development delay
  • Progressive Ataxie
  • Vertical supranuclear gaze palsy
  • Epilepsie
  • Cataplexy

Juvenil
(Age of onset: 6-15 years)

  • Hepatosplenomegaly or isolated splenomegaly
  • Cognitive decline
  • Progressive ataxia
  • Vertical supranuclear gaze palsy
  • Dystonia
  • Epilepsy
  • Cataplexy

Adult
(Age of onset: > 15 years)

  • Cognitive decline
  • Psychiatric symptoms
  • Vertical supranuclear gaze palsy
  • Progressive ataxia
  • Dystonia

Diagnostics:

  • Oxysterols in plasma (screeningparameter, also elevated in LAL-D and ASMD)
  • Lyso-sphingomyelin 509
  • Molecular genetic analysis of NPC1 / NPC2 Gene

Therapy:
Miglustat (Substrate reduction therapy)

Current Studies

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

Niemann-Pick Selbsthilfegruppe Deutschland e.V.
https://www.niemann-pick.de/

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

Literature

Belmatoug, N., A. Burlina, P. Giraldo, C. J. Hendriksz, D. J. Kuter, E. Mengel, and G. M. Pastores. 

Gastrointestinal Disturbances and Their Management in Miglustat-Treated Patients

Bonnot, O., C. S. Gama, E. Mengel, M. Pineda, M. T. Vanier, L. Watson, M. Watissee, B. Schwierin, and M. C. Patterson. "Psychiatric and Neurological Symptoms in Patients with Niemann-Pick Disease Type C (Np-C).

Psychiatric and Neurological Symptoms in Patients with Niemann-Pick Disease Type C (Np-C): Findings from the International Npc Registry

Bremova, T., V. Malinova, Y. Amraoui, E. Mengel, J. Reinke, M. Kolnikova, and M. Strupp.

Acetyl-Dl-Leucine in Niemann-Pick Type C: A Case Series

Cortina-Borja, M., D. Te Vruchte, E. Mengel, Y. Amraoui, J. Imrie, S. A. Jones, I. Dali C, P. Fineran, T. Kirkegaard, H. Runz, R. Lachmann, T. Bremova-Ertl, M. Strupp, and F. M. Platt.

Annual Severity Increment Score as a Tool for Stratifying Patients with Niemann-Pick Disease Type C and for Recruitment to Clinical Trials.

Geberhiwot, T., A. Moro, A. Dardis, U. Ramaswami, S. Sirrs, M. P. Marfa, M. T. Vanier, M. Walterfang, S. Bolton, C. Dawson, B. Heron, M. Stampfer, J. Imrie, C. Hendriksz, P. Gissen, E. Crushell, M. J. Coll, Y. Nadjar, H. Klunemann, E. Mengel, M. Hrebicek, S. A. Jones, D. Ory, B. Bembi, M. Patterson, and Registry International Niemann-Pick Disease.

Consensus Clinical Management Guidelines for Niemann-Pick Disease Type C

Group, Np- C. Guidelines Working, J. E. Wraith, M. R. Baumgartner, B. Bembi, A. Covanis, T. Levade, E. Mengel, M. Pineda, F. Sedel, M. Topcu, M. T. Vanier, H. Widner, F. A. Wijburg, and M. C. Patterson

Recommendations on the Diagnosis and Management of Niemann-Pick Disease Type C

Maekawa, M., A. Narita, I. Jinnoh, T. Iida, T. Marquardt, E. Mengel, Y. Eto, P. T. Clayton, H. Yamaguchi, and N. Mano

Diagnostic Performance Evaluation of Sulfate-Conjugated Cholesterol Metabolites as Urinary Biomarkers of Niemann-Pick Disease Type C

Mengel, E., H. H. Klunemann, C. M. Lourenco, C. J. Hendriksz, F. Sedel, M. Walterfang, and S. A. Kolb

Niemann-Pick Disease Type C Symptomatology: An Expert-Based Clinical Description

Mengel, E., M. Pineda, C. J. Hendriksz, M. Walterfang, J. V. Torres, and S. A. Kolb

Differences in Niemann-Pick Disease Type C Symptomatology Observed in Patients of Different Ages

Patterson, M. C., E. Mengel, M. T. Vanier, B. Schwierin, A. Muller, P. Cornelisse, M. Pineda, and N. P. C. Registry investigators

Stable or Improved Neurological Manifestations During Miglustat Therapy in Patients from the International Disease Registry for Niemann-Pick Disease Type C: An Observational Cohort Study

Patterson, M. C., E. Mengel, F. A. Wijburg, A. Muller, B. Schwierin, H. Drevon, M. T. Vanier, and M. Pineda.

Disease and Patient Characteristics in Np-C Patients: Findings from an International Disease Registry

Pineda, M., E. Mengel, H. Jahnova, B. Heron, J. Imrie, C. M. Lourenco, V. van der Linden, P. Karimzadeh, V. Valayannopoulos, P. Jesina, J. V. Torres, and S. A. Kolb

A Suspicion Index to Aid Screening of Early-Onset Niemann-Pick Disease Type C (Np-C)

Pineda, M., J. E. Wraith, E. Mengel, F. Sedel, W. L. Hwu, M. Rohrbach, B. Bembi, M. Walterfang, G. C. Korenke, T. Marquardt, C. Luzy, R. Giorgino, and M. C. Patterson

Miglustat in Patients with Niemann-Pick Disease Type C (Np-C): A Multicenter Observational Retrospective Cohort Study

Reunert, J., A. S. Lotz-Havla, G. Polo, F. Kannenberg, M. Fobker, M. Griese, E. Mengel, A. C. Muntau, P. Schnabel, O. Sommerburg, I. Borggraefe, A. Dardis, A. P. Burlina, M. A. Mall, G. Ciana, B. Bembi, A. B. Burlina, and T. Marquardt

Niemann-Pick Type C-2 Disease: Identification by Analysis of Plasma Cholestane-3beta,5alpha,6beta-Triol and Further Insight into the Clinical Phenotype

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

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

Speak, A. O., N. Platt, M. Salio, D. te Vruchte, D. A. Smith, D. Shepherd, N. Veerapen, G. S. Besra, N. M. Yanjanin, L. Simmons, J. Imrie, J. E. Wraith, R. H. Lachmann, R. Hartung, H. Runz, E. Mengel, M. Beck, C. J. Hendriksz, F. D. Porter, V. Cerundolo, and F. M. Platt

Invariant Natural Killer T Cells Are Not Affected by Lysosomal Storage in Patients with Niemann-Pick Disease Type C

Speak, A. O., D. Te Vruchte, L. C. Davis, A. J. Morgan, D. A. Smith, N. M. Yanjanin, L. Simmons, R. Hartung, H. Runz, E. Mengel, M. Beck, J. Imrie, E. Jacklin, J. E. Wraith, C. Hendriksz, R. Lachmann, C. Cognet, R. Sidhu, H. Fujiwara, D. S. Ory, A. Galione, F. D. Porter, E. Vivier, and F. M. Platt

Altered Distribution and Function of Natural Killer Cells in Murine and Human Niemann-Pick Disease Type C1

Stampfer, M., S. Theiss, Y. Amraoui, X. Jiang, S. Keller, D. S. Ory, E. Mengel, C. Fischer, and H. Runz

Niemann-Pick Disease Type C Clinical Database: Cognitive and Coordination Deficits Are Early Disease Indicators

Tangemo, C., D. Weber, S. Theiss, E. Mengel, and H. Runz

Niemann-Pick Type C Disease: Characterizing Lipid Levels in Patients with Variant Lysosomal Cholesterol Storage

Valayannopoulos, V., E. Mengel, A. Brassier, and G. Grabowski. "Lysosomal Acid Lipase Deficiency: Expanding Differential Diagnosis

Lysosomal Acid Lipase Deficiency: Expanding Differential Diagnosis

Vom Dahl, S., and E. Mengel

Lysosomal Storage Diseases as Differential Diagnosis of Hepatosplenomegaly

Welford, R. W., M. Garzotti, C. Marques Lourenco, E. Mengel, T. Marquardt, J. Reunert, Y. Amraoui, S. A. Kolb, O. Morand, and P. Groenen

Plasma Lysosphingomyelin Demonstrates Great Potential as a Diagnostic Biomarker for Niemann-Pick Disease Type C in a Retrospective Study

Vruchte D, Speak AO, Wallom KL, Al Eisa N, Smith DA, Hendriksz CJ, Simmons L, Lachmann RH, Cousins A, Hartung R, Mengel E, Runz H, Beck M, Amraoui Y, Imrie J, Jacklin E, Riddick K, Yanjanin NM, Wassif CA, Rolfs A, Rimmele F, Wright N, Taylor C, Ramaswami U, Cox TM, Hastings C, Jiang X, Sidhu R, Ory DS, Arias B, Jeyakumar M, Sillence DJ, Wraith JE, Porter FD, Cortina-Borja M, Platt FM.

Relative acidic compartment volume as a lysosomal storage disorder-associated Biomarker

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 Recommendation for a Diagnostic Guideline for Acid Sphingomyelinase DeficiencyGenet Med 19, no. 9 (Sep 2017)

Mengel, E., B. Bembi, M. Del Toro, F. Deodato, M. Gautschi, S. Grunewald, S. Gronborg, B. Heron, E. M. Maier, A. Roubertie, S. Santra, A. Tylki-Szymanska, S. Day, T. Symonds, S. Hudgens, M. C. Patterson, C. Guldberg, L. Ingemann, N. H. T. Petersen, T. Kirkegaard, and I. Dali C.

Clinical Disease Progression and Biomarkers in Niemann-Pick Disease Type C: A Prospective Cohort Study

Patterson, M. C., E. Mengel, M. T. Vanier, P. Moneuse, D. Rosenberg, and M. Pineda

Treatment Outcomes Following Continuous Miglustat Therapy in Patients with Niemann-Pick Disease Type C: A Final Report of the Npc Registry

At present we have no literature available.