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Test ID: NPCKM    
Niemann-Pick Type C Disease, Known Mutation

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

Carrier testing of individuals for Niemann-Pick disease type C (NPC) when familial mutations have been previously identified


Diagnostic confirmation of NPC when familial mutations have been previously identified


Prenatal testing when 2 familial mutations have been previously identified in an affected family member

Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request

Documentation of the specific familial mutations(s) must be provided with the specimen in order to perform this test.

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

Niemann-Pick type C (NPC) is an inherited disorder of cholesterol transport that results in an accumulation of unesterified cholesterol and lipids in the lysosomal/endosomal system and in various tissues. Although NPC belongs to a group of lysosomal disorders including Niemann-Pick types A and B, these diseases are metabolically and genetically distinct. Niemann-Pick types A and B are caused by mutations in the SMPD1 gene, which encodes the enzyme sphingomyelinase, whereas NPC is caused by mutations in the NPC1 or NPC2 genes.


The incidence of NPC is approximately 1:120,000 to 1:150,000 live births. Age of onset is variable and ranges from the perinatal period to adulthood. Clinical presentation is also highly variable. Infants may present with or without liver disease (hepatosplenomegaly) and respiratory failure. Those without liver failure and pulmonary disease may present with hypotonia and developmental delay. 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. Adult onset NPC is associated with a slower progression and is characterized by neurologic and psychiatric problems.


NPC is inherited in an autosomal recessive manner, in which affected individuals carry 2 mutations in either the NPC1 or NPC2 gene. Most mutations are family specific, although there are 2 mutations in the NPC1 gene which are more common than others. The G992W mutation is common in the French Acadian population of Nova Scotia. The I1061T mutation is the most common mutation worldwide, and is seen in patients of Hispanic and Western European (United Kingdom and France) descent. Full gene sequencing and analysis for large deletions and duplications of the NPC1 and NPC2 genes detect less common disease-causing mutations.


The recommended first-tier test to screen for NPC is a biochemical test measuring cholesterol esterification coupled with filipin staining on a fibroblast specimen, NIEM / Niemann-Pick Type C Detection, Fibroblasts. Molecular testing provides confirmation of a biochemical diagnosis or a basis for carrier testing of family members. Individuals with abnormal biochemical results are more likely to have 2 identifiable mutations by molecular testing.

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.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretative report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order NPCMS / Niemann-Pick Type C, Full Gene Analysis.


Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with Niemann-Pick type C.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.


In addition to disease-related probes, the ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

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

1. NP-C Guidelines Working Group, Wraith JE, Baumgartner MR, et al: Recommendations on the diagnosis and management of Niemann-Pick disease type C. Mol Genet Metab 2009 Sep-Oct;98(1-2):152-65

2. Park WD, O'Brien JF, Lundquist PA, et al: Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1. Hum Mutat 2003 Oct;22(4):313-325

3. Vanier MT: Niemann-Pick disease type C. Orphanet J Rare Dis. 2010 Jun 3;5:16

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test