Familial Chylomicronemia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
13025 APOA5 81479,81479 Order Options and Pricing
APOC2 81479,81479
CREB3L3 81479,81479
GPD1 81479,81479
GPIHBP1 81479,81479
LMF1 81479,81479
LPL 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
13025Genes x (7)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Familial chylomicronemia syndrome (FCS) is characterized by high plasma triglyceride levels resulting from improper breakdown of chylomicron lipoproteins by the LPL enzyme (Brahm and Hegele. 2015. PubMed ID: 25732519; Chait and Eckel. 2019. PubMed ID: 31035285). Triglyceride levels below 1.7 mmol/L (150 mg/dL) are considered normal, while patients with chylomicronemia typically have triglyceride levels over 10 mmol/L (Stroes et al. 2017. PubMed ID: 27998715; Rare Disease Report). The FCS phenotype includes high triglyceride levels and at least one physical manifestation of chylomicronemia. Manifestations of FCS can be severe and life threatening and include primarily debilitating pancreatitis and abdominal pain, hepatosplenomegaly, eruptive xanthomas, and lipemia retinalis. Patients may also feel numbness or tingling and feel fatigued and display cognitive impairment. Laboratory anomalies include chylomicronemia, hyperlipoproteinemia, hypertriglyceridemia, decreased plasma apolipoprotein C-II, and cloudy or pinkish-colored blood (Burnett et al. 2017. PubMed ID: 20301485; Brahm and Hegele. 2015. PubMed ID: 25732519).

The prevalence of FCS is around 1 per million individuals worldwide (Brahm and Hegele. 2015. PubMed ID: 25732519), but in one study of French Canadians, the prevalence was observed to be as high as 200 per million individuals (Gagne et al. 1989. PubMed ID: 2914262). Diagnosis is complicated by several factors. For example, while many patients develop symptoms in childhood, many other patients are not diagnosed until their teens or later as symptoms like recurring pancreatitis and abdominal pain begin to occur more frequently. In addition, secondary causes of hypertriglyceridemia, such as pregnancy, diabetes, alcohol use, lymphoproliferative disorders, estrogen therapy, and use of certain medications including specific serotonin uptake inhibitors and antihypertensive agents, may lead to misdiagnosis of FCS (Burnett et al. 2017. PubMed ID: 20301485; Stroes et al. 2017. PubMed ID: 27998715). Reduced LPL enzyme activity is a key feature of FCS, and functional assays of LPL activity are used for making a diagnosis. However, such assays are not always readily available, and the output of these assays often shows considerable variability (Chait and Eckel. 2019. PubMed ID: 31035285).

Genetic testing has emerged as the preferred method of FCS diagnosis because it allows for identification of the mutated FCS gene and distinguishes FCS from other much more common causes of chylomicronemia such as multifactorial chylomicronemia syndrome (MFCS) and familial partial lipodystrophy (FPLD; Chait and Eckel. 2019. PubMed ID: 31035285). Therapeutic approaches to lowering triglyceride levels vary depending upon the cause of chylomicronemia. Lipid-lowering drugs used to treat other metabolic lipid disorders are ineffective in the treatment of FCS. The current standard of care for FCS involves a strict diet with extremely low levels of fat (<10-15 g/day), low carbohydrates, and little alcohol (Kawashiri et al. 2005. PubMed ID: 16174715).

Genetics

FCS is caused by biallelic pathogenic variants in APOC2 (Fojo et al. 1989. PubMed ID: 2592354), APOA5 (Marcais et al. 2005. PubMed ID: 16200213), GPIHBP1 (Beigneux et al. 2009. PubMed ID:19304573), LMF1 (Peterfy et al. 2007. PubMed ID: 17994020), GPD1 (Joshi et al. 2014. PubMed ID: 24549054)and LPL (Jap et al. 2003. PubMed ID: 12883259). Heterozygous carriers of pathogenic variants in APOA5, GPIHBP1, and LPL may also be at risk for elevated triglyceride levels. Heterozygous variants in the CREB3L3 gene have also been identified in patients with elevated triglycerides and have been associated primarily with a phenotypically similar disorder known as multifactorial chylomicronemia syndrome (MFCS; D'Erasmo et al. 2019. PubMed ID: 31619059, Dron et al. 2020. PubMed ID: 32580631, Lee et al. 2011. PubMed ID: 21666694, Johansen. 2014. PubMed ID: 24503134; Johansen et al. 2012. PubMed ID: 22135386).

The gene products of APOC2, APOA5, GPIHBP1, LMF1, and LPL are all involved in the breakdown of chylomicrons in plasma (Brahm and Hegele. 2015. PubMed ID: 25732519). GPD1 encodes glycerol-3-phosphate dehydrogenase-1, which catalyzes the interconversion of dihydroxyacetone phosphate and glycerol-3-phosphate (G3P); G3P is needed for synthesis of triglycerides (Basel-Vanagaite et al. 2012. PubMed ID: 22226083). CREB3L3 is a transcription factor that regulates expression of genes involved in triglyceride hydrolysis (Lee et al. 2011. PubMed ID: 21666694).

The vast majority of FCS cases are attributed to pathogenic variants in LPL (~95%), followed by APOC2 (~2%), GPIHBP1 (~2%), APOA5, GPD1, and LMF1 (<1%; Burnett et al. 2017. PubMed ID: 20301485; Brahm and Hegele. 2015. PubMed ID: 25732519; Chokshi et al. 2014. PubMed ID: 24793350; Joshi et al. 2014. PubMed ID: 24549054). Variants in CREB3L3 are found frequently in patients with non-monogenic hypertriglyceridemia (Dron et al. 2020. PubMed ID: 32580631) but have also been reported with variable penetrance in patients with autosomal dominant hypertriglyceridemia (Cefalu et al. 2015. PubMed ID: 26427795). Pathogenic loss of function variants in FCS comprise mainly missense, nonsense, and splicing variants, though copy number variants (CNVs) involving APOA5, APOC2, LDL, and GPIHBP1 have been reported in FCS patients (Hegele et al. 2018. PubMed ID: 29748148). In one study of 67 individuals with a clinical diagnosis of FCS, 52 individuals had a confirmed genetic diagnosis of FCS; 5 of the patients were either homozygous or compound heterozygous for CNVs including what may be a recurring deletion in GPIHBP1 that includes exons 3-4 (Hegele et al. 2018. PubMed ID: 29748148). De novo variants have been observed for the FCS genes, but in most cases pathogenic variants are inherited from parental carriers.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Causal or likely causal variants have been identified in up to 77% of patients with a clinical diagnosis of FCS in studies that included nucleotide substitution, short deletion and insertion, and CNV analysis of APOA5, APOC2, GPIHBP1, LMF1, and LPL (Hegele et al. 2018. PubMed ID: 29748148).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with elevated triyglyceride levels and chylomicronemia along with physical manifestations including acute pancreatitis and eruptive xanthomas are candidates for FCS testing. Chylomicronemia is associated with a number of different clinical conditions. Genetic testing can help distinguish FCS from other disorders including multifactorial chylomicronemia syndrome (MFCS) and familial partial lipodystrophy (FPLD) and from secondary causes of hypertriglyceridemia including pregnancy, diabetes, alcohol use, lymphoproliferative disorders, estrogen therapy, and use of certain medications including specific serotonin uptake inhibitors and antihypertensive agents (Chait and Eckel. 2019. PubMed ID: 31035285).

Genes

Official Gene Symbol OMIM ID
APOA5 606368
APOC2 608083
CREB3L3 611998
GPD1 138420
GPIHBP1 612757
LMF1 611761
LPL 609708
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Basel-Vanagaite et al. 2012. PubMed ID: 22226083
  • Beigneux et al. 2009. PubMed ID: 19304573
  • Brahm and Hegele. 2015. PubMed ID: 25732519
  • Burnett et al. 2017. PubMed ID: 20301485
  • Cefalù et al. 2015. PubMed ID: 26427795
  • Chait and Eckel. 2019. PubMed ID: 31035285
  • Chokshi et al. 2014. PubMed ID: 24793350
  • D'Erasmo et al. 2019. PubMed ID: 31619059
  • Dron et al. 2020. PubMed ID: 32580631
  • Fojo et al. 1989. PubMed ID: 2592354
  • Gagné et al. 1989. PubMed ID: 2914262
  • Hegele et al. 2018. PubMed ID: 29748148
  • Jap et al. 2003. PubMed ID: 12883259
  • Johansen et al. 2012. PubMed ID: 22135386
  • Johansen et al. 2014. PubMed ID: 24503134
  • Joshi et al. 2014. PubMed ID: 24549054
  • Kawashiri et al. 2005. PubMed ID: 16174715
  • Lee et al. 2011. PubMed ID: 21666694
  • Marçais et al. 2005. PubMed ID: 16200213
  • Péterfy et al. 2007. PubMed ID: 17994020
  • Rare Disease Report (https://fcs.raredr.com)
  • Stroes et al. 2017. PubMed ID: 27998715

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

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