Interpretive Handbook

Test 9313 :
Niemann-Pick Type C Detection, Fibroblasts

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Niemann-Pick disease type C (NPC)(1) is caused by a defect in cellular cholesterol trafficking that results in the accumulation of unesterified cholesterol in late endosomes/lysosomes. Age of onset is variable and ranges from the perinatal period to adulthood, and clinical presentation is also highly variable. Most individuals are diagnosed during childhood with symptoms including ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, and seizures resulting in death by the second or third decade of life. Infants may present with or without hepatosplenomegaly and respiratory failure. Those without liver and pulmonary disease may present with hypotonia and developmental delay. Adult-onset NPC is associated with a slower progression and is characterized by psychiatric illness, ataxia, dystonia, and speech difficulties.


The incidence of NPC is approximately 1 in 120,000 to 150,000 live births. NPC is an autosomal recessive condition and is caused by mutations in either the NPC1 or NPC2 genes. 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.

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of Niemann-Pick disease type C

Interpretation Provides information to assist in interpretation of the test results

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.

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.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Online Mendelian Inheritance in Man (OMIM): entry 257220

2. Patterson M: Niemann-Pick Disease type C. Available from:; Reviewed July 18, 2013

3. 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

4. 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

5. 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