Other Lipid Disorders

Genetic testing can be important in screening, diagnosis, and potentially in treatment of lipid disorders, particularly for familial hypercholesterolemia (FH), familial chylomicronemia syndrome (FCS) and sitosterolemia.


Familial chylomicronemia syndrome is a rare genetic disease characterized by the build up of chylomicrons (chylomicronemia), the largest lipoprotein particle, which are responsible for transporting dietary fat and cholesterol. FCS occurs in approximately 1 in 1,000,000 individuals worldwide and is characterized by recurrent pancreatitis and severe hypertryglyceridemia (leading to eruptive xanthomas and lactescence of the plasma). Due to the rarity of the condition, the clinical progression of FCS is not well understood.  FCS may also be underdiagnosed, as high levels of triglycerides may be attributed to other causes before a proper diagnosis is made.  Most cases present in in childhood or adolescence; however, patients can present in adulthood.  FCS is inherited in an autosomal recessive manner. The FCSNext test is a 5 gene panel that analyzes genes most commonly associated with FCS. The test can be an effective way of identifying at-risk individuals or confirming a diagnosis. This allows for better individualized disease management and treatment decisions. 


Sitosterolemia is a rare autosomal recessively inherited lipid metabolic disorder that can lead to an increased risk of coronary artery disease and heart attack. Sitosterolemia occurs in approximately 1 in 50,000 individuals worldwide. Sitosterolemia patients develop hypercholesterolemia, tendon and tuberous xanthomas, premature development of atherosclerosis, and abnormal hematologic and liver function test results. The majority of patients are diagnosed in childhood. Our sitosterolemia test is a 2 gene panel that analyzes genes most commonly associated with sitosterolemia. The test can be an effective way of identifying at-risk individuals or confirming a diagnosis. This allows for better individualized disease management and treatment decisions.  

There is also an option to choose from an 18 gene lipid menu to customize a test using our supplemental order form. This customizable form will give you the ability to test for the following rare lipid disorders:

Familial HDL deficiency

Lysosomal acid lipase deficiency

LCAT deficiency/Fish-eye disease

Hyperlipoproteinemia type III

Cerebrotendinous xanthomastosis (CTX)

Apolipoprotein C-III deficiency


Quick Reference
Test Code: 8680 Test Name: FHNext® TAT 14-21 days Genes: 4
Test Code: 9520 Test Name: CustomNext-Cardio® TAT 14-21 days Genes: 167
Test Code: 8930 Test Name: Sitosterolemia TAT 14-21 days Genes: 2
Test Code: 8920 Test Name: FCSNext™ TAT 14-21 days Genes: 5

Ordering Options

We offer family variant testing at no additional cost

for all blood relatives of patients who undergo full single gene sequencing, multigene panel testing or exome sequencing at Ambry Genetics and are found to have a pathogenic or likely pathogenic variant. No-cost testing of blood relatives must be completed within 90 days of the original report date. Whenever possible, more closely related relatives should be tested before more distant relatives.

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Why Is This Important?

Knowing if your patient has a lipid disorder can help you determine their future coronary artery disease risk and guide your medical management recommendations. Key benefits include:

  1. Confirm a diagnosis, particularly when clinical criteria are unclear or borderline in an individual
  2. Help tailor medical treatment
  3. Clarify risks to family members, including the inheritance pattern

When To Consider Testing

  • Genetic testing for FCS is recommended when patient has:1
    • TG/TC ratio > 5 mg/dL
    • History of pancreatitis
    • Symptoms < 40y
  • Genetic testing for sitosterolemia is recommended when patient exhibits these symptoms:
    • Tendon and tuberous xanthomas (build-up of yellowish cholesterol rich material over joints)
    • Hemolysis (destruction of red blood cells) and platelet abnormalities
    • Early coronary atherosclerosis due to plaque and fat build up
    • Some patients have high cholesterol with no family history of it

Mutation Distribution and Detection Rates

The FCSNext and sitosterolemia tests are designed and validated to be capable of detecting >99% of described mutations in the genes represented on the tests (analytical sensitivity). The clinical sensitivity of the FCSNext and sitosterolemia test may vary widely according to the specific clinical and family history. 

Test Description

The FCSNext is a comprehensive analysis of 5 genes associated with Familial Chylomicronemia. The Sitosterolemia test is a comprehensive analysis of 2 genes associated with sitosterolemia. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, and is followed by polymerase chain reaction (PCR) and Next-Generation sequencing. Additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Potentially homozygous variants, variants in regions complicated by pseudogene interference, and variant calls not satisfying depth of coverage and variant allele frequency quality thresholds are verified by Sanger sequencing. This assay targets all coding domains, and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis is performed for all genes using a custom pipeline based on read-depth from NGS data followed by a confirmatory orthogonal method, as needed. Exon-level resolution may not be achieved for every gene.

1.Stroes E et al. Diagnostic algorithm familial chylomicronemia syndrome.  Atheroscler Suppl. 2017 Jan;23:1-7. doi: 10.1016/j.atherosclerosissup.2016.10.002. Epub 2016 Dec 18.


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