Neonatal and infantile presentations of NPC are most commonly nonspecific and may go unrecognized. [centogene.com]

Isolated splenomegaly may be the presenting symptom in some adolescents or adults. [rarediseases.org]

NPC disease presentation during the neonatal period varies from subject to subject, with the commonest presentation being prolonged jaundice and mild hepatosplenomegaly. [ojrd.biomedcentral.com]

Classification level: Disorder Synonym(s): - Prevalence: 1-9 / 100 000 Inheritance: Autosomal recessive Age of onset: All ages ICD-10: E75.2 OMIM: 257220 607625 UMLS: C0220756 MeSH: D052556 GARD: - MedDRA: - The documents contained in this web site are presented [orpha.net]

• Gaucher Disease

  H.: Isolation and characterisation of the main splenic glycolipids in the normal organ and Gaucher's disease: evidence for the site of the metabolic block. J. Neuropath. exp. [link.springer.com]

  […] and infantile presentations: Biliary atresia Congenital infections Alpha-1-antitrypsin deficiency Tyrosinemia Malignancies (leukemia, lymphoma, histiocytosis) Other storage diseases (e.g., Gaucher disease, Niemann-Pick disease type A, Niemann-Pick disease [centogene.com]

  Food and Drug Administration (FDA) has not approved miglustat for the treatment of individuals with NPC, although the drug is approved for the treatment of another lysosomal storage disease known as Gaucher disease. [rarediseases.org]

  (same storage cells) or Gaucher disease. [ojrd.biomedcentral.com]

• Weakness

  Cataplexy is characterized by a sudden loss of muscle tone and strength that can cause a sudden head drop, a weak, rubbery sensation in the legs, or in severe cases collapse. [rarediseases.org]

• Splenomegaly

  […] definition Niemann-Pick disease type C (NP-C) is a lysosomal lipid storage disease (see this term) characterized by variable clinical signs, depending on the age of onset, such as prolonged unexplained neonatal jaundice or cholestasis, isolated unexplained splenomegaly [orpha.net]

  Isolated splenomegaly may be the presenting symptom in some adolescents or adults. [rarediseases.org]

  Associated splenomegaly is a useful orientation sign. In case of isolated splenomegaly or hepatosplenomegaly, NP-C should be considered as a possible cause. [ncbi.nlm.nih.gov]

  New mutation described in a young woman with splenomegaly, diagnosed with Niemann-Pick disease type C. Medicina Clínica 2016: 22. LÓPEZ, M., KLEIN, A., DIMBIL, U. & SCOTT, M. 2011. [revista.jdc.edu.co]

• Insomnia

  Insomnia and other sleep problems should be treated with melatonin, and if needed nocturnal sedatives. [rarediseases.org]

  Melatonin may be used to treat insomnia. Patients with a slow disease course may benefit from special schooling for handicapped children. [ncbi.nlm.nih.gov]

• Confusion

  Cataplexy ranges from subtle signs (minor head-drop or falls, often confused with seizures) to full collapse in response to humorous stimuli [ 27 ]. [ncbi.nlm.nih.gov]

• Slurred Speech

  Neurological signs and symptoms include cerebellar ataxia (unsteady walking with uncoordinated limb movements), dysarthria (slurred speech), dysphagia (difficulty in swallowing), tremor, epilepsy (both partial and generalized), vertical supranuclear palsy [en.wikipedia.org]

Papandreou A, Gissen P: Diagnostic workup and management of patients with suspected Niemann-Pick type C disease. Therapeutic advances in neurological disorders 2016;9(3):216-229. [rarediseases.org]

Type B Several treatment options, including bone marrow transplants, enzyme replacement therapy, and gene therapy have been used. Research is ongoing to determine the effectiveness of these treatments. Type C Physical therapy helps with mobility. [healthline.com]

In 2009, the European Medicines Agency approved the use of Zavesca© for the treatment of progressive neurological manifestations in adult and paediatric patients with NP-C. [npuk.org]

Several other treatment strategies are under investigation in cell culture and animal models of NPC. [en.wikipedia.org]

Standard Therapies Treatment Treatment of NPC may require the coordinated efforts of a team of specialists. [rarediseases.org]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

Parents should talk to their child’s physician and medical team about the specific symptoms and overall prognosis. In perinatal NPC, the accumulation of fluid in the fetal abdomen (fetal ascites) may be present and persist after birth. [rarediseases.org]

[…] a potential target.[34] Neural stem cells have also been investigated in an animal model, and clear evidence of life extension in the mouse model has been shown.[35] Low cholesterol diets are often used,[36] but there is no evidence of efficacy.[37] Prognosis [en.wikipedia.org]

NPC disease severity score Statements #12: NPC-specific disease severity scores are useful adjuncts to clinical judgement in assessing disease burden, response to therapy and determining prognosis. [ojrd.biomedcentral.com]

The prognosis largely correlates with the age at onset of the neurological manifestations. [ncbi.nlm.nih.gov]

Etiology Mutations in either of the two genes, NPC1 or NPC2, may cause the disease [ 13 - 16 ]. [ncbi.nlm.nih.gov]

Defintion and epidemiology Definition of NPC Statement #1: NPC is a progressive and life limiting autosomal recessive disorder caused by mutations in either the NPC1 or NPC2 gene. [ojrd.biomedcentral.com]

Epidemiology NP-C (either NP-C1 or NP-C2) shows autosomal recessive inheritance and is panethnic. [ncbi.nlm.nih.gov]

The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):83-7. Review. Vance JE. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett. 2006 Oct 9;580(23):5518-24. Epub 2006 Jun 15. [ghr.nlm.nih.gov]

This couple is the most likely origin for the type D variant.[10] Pathophysiology[edit] Niemann–Pick type C is biochemically, genetically and clinically distinct from Niemann–Pick Types A or and B. [en.wikipedia.org]

The exact functions of the NPC1 and NPC2 proteins are still unclear [ 10 - 12, 56, 57 ], which greatly complicates understanding of the pathophysiology. [ncbi.nlm.nih.gov]

References related to a single topic (i.e., Epidemiology, Genetics, Pathophysiology, Clinical Diagnosis, Laboratory, Imaging, Therapy, Recommendations) were pulled together and the GDG was divided into subgroups aimed to critically appraise references [ojrd.biomedcentral.com]

It works by preventing your body from producing fatty substances so that less of it will build up in your body. In this case, the fatty substance is cholesterol. Type A Some children with the type A form of Niemann-Pick live to the age of 4. [healthline.com]

Mutations in these genes lead to a shortage of functional protein, which prevents movement of cholesterol and other lipids, leading to their accumulation in cells. [ghr.nlm.nih.gov]

Physiotherapy is useful in the management of spasticity and the prevention of contractures. Melatonin may be used to treat insomnia. Patients with a slow disease course may benefit from special schooling for handicapped children. [ncbi.nlm.nih.gov]