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Test ID: NPCZ Niemann-Pick Type C Disease, Full Gene Analysis, Varies

Reporting Name

NPC1/NPC2 Genes, Full Gene Analysis

Useful For

Second-tier test for confirming a biochemical diagnosis of Niemann-Pick type C (NPC)


Carrier testing of individuals with a family history of NPC when an affected individual is not available for testing or disease-causing mutations have not been identified

Clinical Information

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 in 120,000 to 1 in 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 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 that 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.


All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

Analytic Time

14 days

Day(s) and Time(s) Performed

Performed weekly, Varies

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. 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

3. 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

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

Method Name

Polymerase Chain Reaction (PCR) Amplification Followed by DNA Sequencing/Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)

Specimen Type


Shipping Instructions

Specimen preferred to arrive within 96 hours of draw.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.


Submit only 1 of the following specimens:


Specimen Type: Whole blood


Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated


Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours


Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reference Values

An interpretive report will be provided.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81404-NPC2 (Niemann-Pick disease, type C2 [epididymal secretory protein E1]) (eg, Niemann-Pick disease type C2), full gene sequence    

81406-NPC1 (Niemann-Pick disease, type C1) (eg, Niemann-Pick disease), full gene sequence


Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
NPCZ NPC1/NPC2 Genes, Full Gene Analysis 94211-0


Result ID Test Result Name Result LOINC Value
53533 Result Summary 50397-9
53534 Result 82939-0
53535 Interpretation 69047-9
53536 Additional Information 48767-8
53537 Specimen 31208-2
53538 Source 31208-2
53539 Released By 18771-6


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

3. If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen.