Niemann-Pick Type C Detection, Fibroblasts
Detection of a unique form of type C Niemann-Pick disease
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Diagnostic test for Niemann-Pick type C. Not recommended for carrier detection. Cholesterol esterification followed by filipin staining, if positive.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal storage disorder caused by a defect in cellular cholesterol trafficking due to mutations in either the NPC1 or NPC2 gene. The resulting accumulation of unesterified cholesterol in late endosomes/lysosomes interrupts the normal functioning of cells, tissues, and organs. There are 2 other forms of Niemann-Pick disease, types A and B, resulting from a deficiency of sphingomyelinase and mutations in the SMPD1 gene.
Clinical features of NPC vary widely depending on the age of onset, which can range from the neonatal period to adulthood. Most cases present in middle to late childhood with a classic disease course. Hepatosplenomegaly may be the initial symptom of the disease. Clinical manifestations include vertical gaze palsy, ataxia, speech and swallowing difficulties, cognitive problems, and dementia. In early onset cases, severe, lethal neonatal liver disease and hydrops fetalis can occur. Common features of adult onset NPC include cognitive decline leading to dementia, psychiatric illness, ataxia, dystonia, and speech difficulties. Currently, treatment and management are supportive only.
Biochemical testing that demonstrates impaired cholesterol esterification and positive filipin staining in cultured fibroblasts is diagnostic for NPC. About 95% of individuals with NPC have mutations in the NPC1 gene. Mutations may also be identified in the NPC2 gene; see NPCMS / Niemann-Pick Type C, Full Gene Analysis.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
If the results indicate that the patient's cultured fibroblasts esterify cholesterol at a level which is <10% of normal cultured fibroblasts and when filipin staining shows excessive storage of free cholesterol, it will be stated that the patient is positive for Niemann-Pick type C disease. All samples will be stained by filipin to see if a milder biochemical phenotype is the likely cause of the Niemann-Pick disease-like clinical picture.
Values expected in Niemann-Pick disease type C are <10% of that found in normal cultured fibroblasts.
Values between 10% and 80% of normal will have to be judged on other diagnostic criteria.
All values will be followed up by filipin staining for cholesterol.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Biochemical testing is unreliable for Niemann-Pick disease type C carrier detection.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Patterson M: Niemann-Pick Disease type C. Available from: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=npc; Reviewed July 18, 2013
2. Enns GM, Steiner RD, Cowan TM: Lysosomal Disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. New York, McGraw-Hill Medical Division, 2009, pp 740
3. Bauer P, Balding DJ, Klunemann HH, et al: Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study. Hum Mol Gen 2013;22(21):4349-4356
4. Patterson MC, Mengel E, Wijburg FA, et al: Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis 2013;8:12