Diagnosis guide for clinicians

Familial chylomicronemia syndrome (FCS): when to suspect it and what to test

Not a doctor or health care professional? This page is for clinicians.Go to the patient version

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder in which biallelic pathogenic variants in LPL, or in 1 of 4 related genes, profoundly reduce lipoprotein lipase activity and cause extreme, sustained hypertriglyceridemia, according to a National Lipid Association expert review.Source NLA expert clinical review

GeneReviews says lipoprotein lipase deficiency, the most common form of FCS, usually presents in childhood with abdominal pain, recurrent acute pancreatitis, eruptive xanthomata and hepatosplenomegaly, while some people present for the first time during pregnancy.

Source GeneReviews

In the UK FCS national registry, the median age at symptom onset was 15 years and the median age at diagnosis was 22 years, a delay of 7 years.

Source UK FCS national registry

885mg/dL or 1000mg/dLPersistent triglyceride level that defines severe hypertriglyceridemia in FCS (10mmol/L or more, or 1000mg/dL or more, depending on region and units)NLA expert clinical review

5 genesLPL, APOC2, APOA5, GPIHBP1 and LMF1; FCS is caused by biallelic pathogenic variants (autosomal recessive)GeneReviews

7 yearsGap between median age at symptom onset and at diagnosis among 74 patients with FCS in the UK national registryUK FCS national registry

E78.3ICD-10-CM code, HyperchylomicronemiaNLM ICD-10-CM lookup

Orphanet recordORPHA:444490 ↗

Inheritance

Autosomal recessive

Age of onset

Infancy, Childhood, Adolescent, Adult

Prevalence

1 to 9 per 1,000,000 annual incidence, United States
1 to 9 per 1,000,000 point prevalence, Europe

Live from Orphanet (INSERM) via Orphadata, licensed CC BY 4.0, data version 2026-06-23.

Print the one-page checklist →

Patterns to test Red flags Often mistaken for What to test Family screening ICD-10 codes Once confirmed For the patient

Patterns that should prompt a test for Familial chylomicronemia syndrome (FCS)

Each sign below is common on its own, which is why Familial chylomicronemia syndrome (FCS) is missed. Published studies describe these combinations as the picture to act on. Rows are ordered from the highest published figure to the lowest, within each kind of measure.

Where testing finds it

Share of each screened or biopsied group found to have Familial chylomicronemia syndrome (FCS), from the cited studies. A bar spans the lowest to the highest published figure.

1
History of chylomicronemia+Persistence despite control of secondary causes and conventional treatment
413 Caucasian patients with a history of chylomicronemia studied by Quebec and Houston authors, 65 of whom (15.7%) met criteria for persistent chylomicronemia
Of the 65 with persistent chylomicronemia, 39 carried a biallelic combination of pathogenic variants (60%, our division of the reported counts) (Brisson 2026).Brisson 2026 score comparison
60%
2
Severe hypertriglyceridemia+Sequencing of the FCS genes
245 patients with severe hypertriglyceridemia sequenced in the Dyslipidemia Registry of the Spanish Atherosclerosis Society
Twenty had FCS with biallelic pathogenic or likely pathogenic variants (8.2%, our division of the reported counts), and 1 more had an FCS phenotype with biallelic variants of uncertain significance (Ariza 2025).Ariza 2025 Spanish registry
8.2%
3
Severely raised triglycerides+Referral to a clinic that manages them
Patients referred to clinics that manage severely elevated triglycerides, as summarized by NORD
FCS is thought to be the cause in 1% to 2% of these patients (NORD report, citing Baass and colleagues).NORD report
1% to 2%
4
Severe hypertriglyceridemia+Sequencing of LPL, APOC2, GPIHBP1, APOA5 and LMF1
563 patients with severe hypertriglyceridemia in 2 cohorts sequenced by a Western University group
Biallelic rare variants were found in 1.1%, heterozygous rare variants in 14.4% and a high polygenic risk score in 32.0% (Dron 2019).Dron 2019 genetic study
1.1%
5
Triglycerides of 1000mg/dL or more (chylomicronemia)+Genetic testing for biallelic variants
Patients with chylomicronemia in general, as estimated by the joint NLA and ASPC consensus
Only about 0.1% to 1% of patients with chylomicronemia have FCS; the consensus puts triglycerides of 1000mg/dL or more at about 1 in 500 US adults (Saadatagah 2025).NLA and ASPC consensus
0.1% to 1%

How often diagnosed patients show it

Share of patients already diagnosed who had the finding, in the group named on each row. Groups differ by age and type, so read each row with its group.

1
Severe hypertriglyceridemia+Post-heparin LPL activity below 25.1mU/mL
14 patients with genetically confirmed FCS (9 in a derivation group and 5 in a validation group) studied in Malaga and other Spanish centers
All 14 had LPL activity below the cut-off, with no overlap with the multifactorial chylomicronemia groups (Rioja 2023).Rioja 2023 LPL activity study
100%
2
LDL cholesterol under 39.2mg/dL+Body mass index under 26.1kg/m2+History of pancreatitis
49 patients with genetically confirmed FCS and 105 with multifactorial severe hypertriglyceridemia from 2 volanesorsen trials, in an Akcea and Ionis funded analysis
Having at least 2 of these 3 identified 91.8% of the patients with FCS, with 90.6% specificity and 91.0% accuracy (O'Dea 2019).O'Dea 2019 clinical profiles
91.8%
3
Fasting triglycerides above 885mg/dL on repeated tests+European FCS score of 10 or more
Patients with FCS in 3 studies: 53 in the original European cohorts, 75 in the UK and 35 in Montreal
A score of 10 or more was reached by 88% (Moulin 2018), 96% (Bashir 2024) and 74.3% (Paquette 2026); specificity against multifactorial chylomicronemia was 85%, 75% and 97.0%.Moulin 2018 FCS score
74.3% to 96%
4
Persistent triglycerides above 880mg/dL+North American FCS score of 45 or more
Patients with genetically confirmed FCS in 4 studies: 66 in the Balance trial, 38 in Izmir, 35 in Montreal and the Western University clinic registry
A score of 45 or more was reached by 95.5% (Brown 2025, with Ionis authors), 88.9% (Hegele 2025), 84.2% (Simsir 2026) and 74.3% (Paquette 2026).Hegele 2025 North American FCS score
74.3% to 95.5%
5
Severe hypertriglyceridemia+Unexplained abdominal pain
74 patients with FCS in the UK registry and 25 in Montreal
Unexplained abdominal pain was recorded in 84% against 52% with multifactorial chylomicronemia (UK registry), and abdominal pain in 63% against 19% (Paquette 2019).UK FCS national registry
63% to 84%
6
Severe hypertriglyceridemia+Acute pancreatitis
74 patients with FCS in the UK registry, 66 adults in the APPROACH trial, 38 in Izmir and 25 in Montreal
Acute pancreatitis had occurred in 84% (UK registry), 76% (Blom 2018), 86.8% (Simsir 2026) and 60% (Paquette 2019); the UK authors pooled earlier studies at 70.7% in FCS against 16.3% in multifactorial chylomicronemia.UK FCS national registry
60% to 86.8%
7
Acute pancreatitis with severe hypertriglyceridemia+A second or later episode
Patients with FCS in the UK registry and in Montreal, and earlier studies pooled by the UK authors
Recurrent acute pancreatitis was reported in 92% of the 62 patients with FCS who had had acute pancreatitis (57 patients), against 63% of the 48 with multifactorial chylomicronemia who had had it (UK registry); multiple episodes at 48% of 25 patients (Paquette 2019); 54.6% in pooled earlier studies.UK FCS national registry
48% to 92%
8
Severe hypertriglyceridemia+No diabetes, hypertension or obesity
74 patients with FCS and 80 with multifactorial chylomicronemia in the UK registry
None of these 3 features was present in 64% of patients with FCS against 29% with the multifactorial form (UK registry).UK FCS national registry
64%
9
Severe hypertriglyceridemia+Body mass index under 25kg/m2
74 patients with FCS and 80 with multifactorial chylomicronemia in the UK registry
Body mass index was under 25kg/m2 in 59% of patients with FCS against 20% with the multifactorial form (UK registry).UK FCS national registry
59%
10
Lactescent serum in a child+Hepatosplenomegaly, eruptive xanthomas or lipemia retinalis
50 published pediatric cases of FCS from LPL variants, aged a few days to 16 years, reviewed in a 2022 editorial
Physical signs were seen in 26 of 50 (52%, our division of the reported counts); 17 had no symptoms at presentation and 14 (28%) had pancreatitis or abdominal pain (Ariza 2022).Ariza 2022 pediatric editorial
52%
11
Triglycerides above 2000mg/dL+Eruptive xanthomas
People with lipoprotein lipase deficiency described in GeneReviews and MedlinePlus Genetics
About 50% have eruptive xanthomas, which can appear rapidly when triglycerides exceed 2000mg/dL (GeneReviews 2026).GeneReviews
50%
12
Chylomicronemia in a pregnant woman+Acute pancreatitis during pregnancy
Twenty women with FCS (biallelic variants or an elevated clinical score) among 49 European and North American women with chylomicronemia whose 116 pregnancies were reviewed
At least 1 episode during pregnancy occurred in 42% of the women with FCS against 10% of those with multifactorial chylomicronemia (Larouche 2026).Larouche 2026 pregnancy study
42%
13
Chylomicronemia in an infant+Symptoms before age 1 year
Children with lipoprotein lipase deficiency described in GeneReviews
Approximately 25% of affected children develop symptoms before age 1 year, and the majority before age 10 years (GeneReviews 2026).GeneReviews
25%

Also described, without a comparable figure

Lipemia retinalis + Triglycerides above 4000mg/dL: No percentage was found; GeneReviews marks it as common but only when triglycerides exceed 4000mg/dL, and says it is reversible and does not affect vision.GeneReviews
Severe hypertriglyceridemia + Affected sibling or parental consanguinity: No frequency for this combination was found; GeneReviews says a family history consistent with recessive inheritance supports the diagnosis and its absence does not preclude it.GeneReviews
Intermittent severe hypertriglyceridemia + Another autoimmune condition + Inconclusive genetic testing: No frequency was found; the panel links this picture, and adult onset, to antibodies against GPIHBP1 (Aguilar-Salinas 2025).Latin American Delphi consensus

These figures describe published study groups. They are not the chance that any one patient has Familial chylomicronemia syndrome (FCS), and bars whose ranges overlap are not in a settled order.

Red flags for Familial chylomicronemia syndrome (FCS)

What the cited sources describe, grouped by life stage and organ. Each line links to its source.

Triglycerides and the blood sample

Persistent severe hypertriglyceridemia, defined by a National Lipid Association expert review as 10mmol/L or more (885mg/dL or more), or 1000mg/dL or more depending on region, with no secondary factors and resistance to conventional lipid-lowering therapies.NLA expert clinical review
Plasma triglycerides above 2000mg/dL in the untreated state, regardless of fasting status, which GeneReviews lists as a supportive laboratory finding for lipoprotein lipase deficiency.GeneReviews
Milky (lactescent or lipemic) plasma, which GeneReviews attributes to impaired clearance of chylomicrons.GeneReviews
In the UK registry, all 74 patients with FCS had triglycerides consistently above 10mmol/L (885mg/dL) on at least 3 tests spaced at least 1 month apart, and 99% exceeded 20mmol/L (1770mg/dL) at least once.UK FCS national registry
A Latin American multi-society Delphi consensus lists a consistent lipid profile: normal or low direct LDL cholesterol, low HDL cholesterol, a triglyceride to total cholesterol ratio above 5 and low to normal apolipoprotein B.Latin American Delphi consensus
A pediatric editorial describes a child with no symptoms whose FCS was found because serum drawn for a coagulation work-up looked milky.Ariza 2022 pediatric editorial

Pancreas and abdomen

Abdominal pain, present in nearly all affected people per GeneReviews, usually mid-epigastric with radiation to the back; it may mimic an acute abdomen and often leads to unnecessary exploratory surgery.GeneReviews
Acute pancreatitis had occurred in 84% of patients with FCS in the UK registry, against 60% of those with multifactorial chylomicronemia syndrome (MCS), and unexplained abdominal pain in 84% against 52%.UK FCS national registry
The median age at the first episode of acute pancreatitis was 24 years in FCS and 33.5 years in MCS in the UK registry.UK FCS national registry
Among 66 adults with FCS entering the APPROACH trial, 76% reported at least 1 lifetime episode of acute pancreatitis.APPROACH baseline data
In a Montreal Clinical Research Institute cohort, pancreatitis had occurred in 60% of 25 patients with genetically confirmed FCS against 6% of 36 with multifactorial chylomicronemia, and multiple episodes in 48% against 3%.Paquette 2019 FCS versus MCS
Acute pancreatitis had occurred in 86.8% of 38 patients with genetically confirmed FCS at Ege University in Izmir, whose median triglyceride level was 3523mg/dL.Turkish single-center cohort
In the IN-FOCUS patient survey, which had Akcea Therapeutics employees among its authors, the 40% of respondents with FCS-related acute pancreatitis reported a lifetime mean of 13 episodes.IN-FOCUS patient survey
A joint National Lipid Association and American Society for Preventive Cardiology consensus names alarm features: recurrent triglyceride-induced acute pancreatitis, recurrent hospitalizations for severe abdominal pain with no other cause, childhood pancreatitis, a family history of triglyceride-induced pancreatitis, and post-heparin LPL activity under 20% of normal.NLA and ASPC consensus

Skin, eyes, liver and spleen

Eruptive xanthomas, seen in about 50% of people with lipoprotein lipase deficiency: small yellow papules over the trunk, buttocks, knees and extensor surfaces of the arms that can appear rapidly when triglycerides exceed 2000mg/dL.GeneReviews
Lipemia retinalis, a pale pink color of the retinal arterioles and venules and often the fundus, which GeneReviews describes when triglycerides exceed 4000mg/dL; it is reversible and vision is not affected.GeneReviews
Hepatosplenomegaly, which GeneReviews says often occurs when triglycerides are markedly increased and can return to normal size within 1 week of lowering them.GeneReviews
Fatigue, dyspnea and cognitive impairment, sometimes called brain fog, are listed with chylomicronemia in the joint consensus.NLA and ASPC consensus
MedlinePlus Genetics lists depression, memory loss and mild intellectual decline as features that resolve when dietary fat levels normalize.MedlinePlus Genetics

Infancy and childhood

GeneReviews reports that approximately 25% of affected children develop symptoms before age 1 year and the majority before age 10 years.GeneReviews
Poor growth in infants and children is marked as common in the GeneReviews feature table.GeneReviews
Of 50 published pediatric cases reviewed in a 2022 editorial, 17 had no symptoms at presentation, with only febrile episodes, vomiting or diarrhea and lactescent serum noted.Ariza 2022 pediatric editorial
Acute pancreatitis or abdominal pain was reported in 14 of those 50 children (28%), and hepatosplenomegaly, eruptive xanthomas or lipemia retinalis in 26; only 1 child failed to thrive.Ariza 2022 pediatric editorial
Orphanet notes that children may be asymptomatic with later onset of symptoms, and lists failure to thrive among the manifestations.Orphanet cross-references

Adulthood and pregnancy

GeneReviews says lipoprotein lipase deficiency should be suspected particularly in people under age 40 years with the clinical and laboratory findings above.GeneReviews
The median age at diagnosis was 24 years among adults in the APPROACH trial, which the authors read as likely underdiagnosis.APPROACH baseline data
A review by Montreal and Western University authors states that the majority of patients with FCS are diagnosed after age 20, often after consulting several physicians.Baass 2020 review
GeneReviews describes chylomicronemia in late adulthood with biallelic APOA5, GPIHBP1 or LMF1 variants, and symptoms that generally develop at age 13 to 60 years with APOC2 deficiency.GeneReviews
In a review of 116 pregnancies in 49 women with chylomicronemia, 42% of the women with FCS (defined by biallelic variants or an elevated clinical score) had at least 1 episode of acute pancreatitis during pregnancy, against 10% of those with MCS.Larouche 2026 pregnancy study

Family history and ancestry

A family history consistent with autosomal recessive inheritance, such as affected siblings or parental consanguinity; GeneReviews adds that the absence of a known family history does not preclude the diagnosis.GeneReviews
The joint consensus calls the term familial misleading, because patients with FCS usually have no family history of chylomicronemia, whereas patients with MCS often have a family history of elevated triglycerides.NLA and ASPC consensus
In the UK registry, FCS was more common in patients of non-European ethnicity (62% of the FCS group, mostly South Asian) and in those with parental consanguinity.UK FCS national registry
GeneReviews reports a much higher prevalence in some areas of Quebec, Canada, 1 in 10,000 to 30,000, from a founder effect.GeneReviews

Familial chylomicronemia syndrome (FCS) is often mistaken for

Diagnoses patients commonly carry first, and why the sources say they are confused.

First diagnosis	Why it is confused
Multifactorial chylomicronemia syndrome (MCS)	The joint NLA and ASPC consensus says only about 0.1% to 1% of patients with chylomicronemia have FCS; MCS shares the triglyceride range and symptoms but most often presents in adulthood with overweight, diabetes or other secondary factors.NLA and ASPC consensus
Poorly controlled diabetes or familial combined hyperlipidemia	NORD says diagnosis is often delayed because FCS is rare and its symptoms overlap with these more common conditions.NORD report
Acute pancreatitis from gallstones or alcohol	The joint consensus ranks severe triglyceride elevation as the third most common cause of acute pancreatitis, after cholelithiasis and excess ethanol consumption.NLA and ASPC consensus
Acute abdomen	GeneReviews notes the pain may be diffuse and mimic an acute abdomen, often leading to unnecessary abdominal exploratory surgery.GeneReviews
Autoimmune chylomicronemia	Antibodies against GPIHBP1 can cause the same picture, and the joint NLA and ASPC consensus also names antibodies against LPL; the Latin American Delphi panel points to intermittent hypertriglyceridemia, inconclusive genetic testing, other autoimmune conditions and adult onset.Latin American Delphi consensus
Partial lipodystrophy, glycogen storage disease or type III hyperlipoproteinemia	NORD lists these among disorders that also raise triglycerides; it notes that type III hyperlipoproteinemia, unlike FCS, is more likely to lead to cardiovascular disease.NORD report
Hypertriglyceridemia in a heterozygous carrier	GeneReviews notes that a few heterozygotes transiently develop severe hypertriglyceridemia in a range that resembles genuine LPL deficiency, but they are generally very responsive to control of secondary factors and to fibrates.GeneReviews

Codes patients often carry before this diagnosis

For spotting the pattern in a problem list or registry. Descriptions are checked daily against NLM's ICD-10-CM service; this is not coding advice.

Pure hyperglyceridemia, mixed hyperlipidemia or hyperlipidemia, unspecified E78.1, E78.2, E78.5

Persistent triglycerides of 10mmol/L (885mg/dL) or more with no secondary factor are where the NLA expert review starts.NLA expert clinical review

Acute pancreatitis: unspecified, other or idiopathic, without necrosis or infection K85.90, K85.80, K85.00

Acute pancreatitis had occurred in 84% of UK registry patients with FCS, at a median age of 24 years for the first episode.UK FCS national registry

Other chronic pancreatitis K86.1

NORD says repeated episodes of acute pancreatitis in undiagnosed or untreated FCS can progress to chronic pancreatitis.NORD report

Unspecified abdominal pain R10.9

Unexplained abdominal pain was recorded in 84% of UK registry patients with FCS.UK FCS national registry

Hepatomegaly with splenomegaly, not elsewhere classified R16.2

Hepatosplenomegaly is one of the clinical findings GeneReviews lists for suspecting LPL deficiency.GeneReviews

Testing for Familial chylomicronemia syndrome (FCS), step by step

The testing order the cited guidance describes, by who it applies to. It summarizes published guidance and is not a plan for any one patient.

Anyone with a triglyceride level of 1000mg/dL or more

Repeat fasting triglycerides
The joint NLA and ASPC consensus defines persistent chylomicronemia as triglycerides of 1000mg/dL or more in more than half of measurements, and describes 3 measurements of 1000mg/dL or more over 6 to 12 weeks after lifestyle management and first-line drug therapy.NLA and ASPC consensus
Look for secondary factors
The joint consensus lists poorly controlled diabetes, obesity, metabolic syndrome, ethanol, diet, hypothyroidism, nephrotic syndrome, pregnancy and medications such as oral estrogens, corticosteroids, retinoids, thiazides, beta blockers, protease inhibitors and second-generation antipsychotics.NLA and ASPC consensus

Persistent severe hypertriglyceridemia

Review the response to standard treatment
The joint consensus describes very little or no response to fibrates or omega-3 fatty acids in FCS and a modest to substantial response in MCS.NLA and ASPC consensus
Read the rest of the lipid panel, weight and history
In an Akcea and Ionis funded analysis of 2 volanesorsen trials, ultracentrifugally measured LDL cholesterol under 39.2mg/dL, body mass index under 26.1kg/m2 and a history of pancreatitis, taken as a set of 3, separated FCS from multifactorial severe hypertriglyceridemia with 91.0% accuracy.O'Dea 2019 clinical profiles
European FCS score (Moulin 2018)
A European expert panel scored fasting triglycerides above 10mmol/L (885mg/dL) on multiple occasions, resistance to standard therapy, young age at onset, lack of secondary factors (except pregnancy and oral estrogens) and a history of acute pancreatitis. A score of 10 or more had 88% sensitivity and 85% specificity in 53 patients with FCS and 52 with MCS. The companion data paper acknowledges medical writing paid for by Akcea Therapeutics.Moulin 2018 FCS score
European score: UK validation
At 10 or more, sensitivity was 96% and specificity 75% among 151 genotyped UK patients, 75 with FCS and 76 with MCS.Bashir 2024 UK score validation
Both scores: Montreal validation
Among 35 patients with FCS and 202 without, the European score at 10 or more had 74.3% sensitivity and 97.0% specificity, and the North American score at 45 or more had 74.3% and 99.0%. The authors concluded that a substantial proportion of patients with FCS are missed and that genetic testing remains essential.Paquette 2026 score validation
North American FCS score (Hegele 2025)
Ten US and Canadian physicians and 1 patient built it from age, onset of hypertriglyceridemia, body mass index, abdominal pain or pancreatitis, secondary factors, triglyceride level, triglyceride to total cholesterol ratio and apolipoprotein B. In the Western University lipid genetics clinic registry, 60 or more had 100.0% specificity and 66.7% sensitivity, and 45 or more had 96.9% and 88.9%. Its funding was not stated in the abstract we read.Hegele 2025 North American FCS score
North American score in a drug trial population
Of 66 patients with genetically confirmed FCS in the Balance trial of olezarsen, 95.5% scored 45 or more and 74.2% scored 60 or more, in an analysis with Ionis employees among its authors.Brown 2025 score in the Balance trial

Suspected FCS

Genetic testing of the 5 genes
GeneReviews establishes LPL deficiency by biallelic pathogenic or likely pathogenic LPL variants, using single-gene testing, a multigene panel that includes the other FCS genes, or exome or genome sequencing. Sequence analysis finds about 96% of LPL pathogenic variants and deletion/duplication analysis about 4%.GeneReviews
Where the variants are found
Of 52 genotyped participants in the APPROACH trial, 41 had biallelic LPL variants; 5 had GPIHBP1 variants, 2 APOA5, 1 LMF1 and 1 APOC2, and 2 were double heterozygotes.Hegele 2018 genotypes in APPROACH
Reading the result
GeneReviews says biallelic variants of uncertain significance, or 1 pathogenic variant with 1 variant of uncertain significance, neither establish nor rule out the diagnosis.GeneReviews
How one registry classified results
The UK registry gave a genetic diagnosis of FCS to homozygotes, compound heterozygotes and double heterozygotes for pathogenic or likely pathogenic variants in the 5 genes, and classed single heterozygous variants and variants of uncertain significance as MCS.UK FCS national registry
Genetic diagnosis or clinical score
GeneReviews says that in practice a diagnostic FCS score serves as a placeholder or surrogate for a positive genetic diagnosis and that regulators will accept either. The Montreal validation above reaches a different emphasis, that genetic testing remains essential.GeneReviews

Clinical picture of FCS with negative or inconclusive genetic testing

Post-heparin LPL activity
The Latin American Delphi panel suggests an LPL activity assay, if available, in this group. It recommends no particular method or threshold and says each laboratory should set its own cut-off.Latin American Delphi consensus
How the assay is done
GeneReviews describes LPL activity measured in plasma taken 10 minutes after intravenous heparin (60U/kg), says absent activity is diagnostic of LPL deficiency, and notes the assay is generally only performed at selected specialist centers.GeneReviews
A published LPL activity cut-off
In a study from Malaga and other Spanish centers, every patient with FCS (9 in the derivation group and 5 in the validation group) had post-heparin LPL activity below 25.1mU/mL, with no overlap with the MCS groups.Rioja 2023 LPL activity study
Autoantibodies
The Delphi panel adds, as a point of good practice, that identifying anti-GPIHBP1 antibodies or whole-exome sequencing are other strategies, and it recommends reconsidering autoimmune chylomicronemia when hypertriglyceridemia is intermittent, genetic results are inconclusive, another autoimmune condition is present or onset is in adulthood.Latin American Delphi consensus

Where testing goes wrong

Triglycerides vary even in genetically confirmed FCS: the joint consensus cites a range of 334 to 6898mg/dL in the Balance trial and says occasional values under 1000mg/dL do not exclude persistent chylomicronemia.NLA and ASPC consensus
A negative gene test does not settle it; the Latin American Delphi panel notes that nearly 25% of patients with clinical features consistent with FCS have a negative genetic test.Latin American Delphi consensus
Sequencing alone can miss a variant; GeneReviews notes that exon or whole-gene deletions and duplications are typically not detected by sequence analysis.GeneReviews
The clinical scores can miss patients: in the Montreal validation, the North American score at 60 or more had 100.0% specificity but 37.1% sensitivity.Paquette 2026 score validation
The scores do not agree with each other; among 26 people with persistent chylomicronemia and no biallelic variants, 20 met the French Canadian threshold, 16 the European, 7 the North American at 45 and 1 at 60.Brisson 2026 score comparison
The UK validation of the European score found a body mass index over 30kg/m2 was a negative predictor, and non-European ethnicity, parental consanguinity, a body mass index under 25kg/m2 and recurrent pancreatitis were positive predictors, but adding them did not improve the score.Bashir 2024 UK score validation
Pregnancy and oral estrogens are the stated exceptions to the secondary factors item in the European score, and the Delphi panel's reproduction of the score asks for a repeat test after delivery when the diagnosis is made during pregnancy.Latin American Delphi consensus
Normal weight is not required; the Delphi panel notes that both normal-weight and overweight people can have FCS.Latin American Delphi consensus
Diabetes does not exclude FCS: 26% of UK registry patients with FCS had diabetes, against 56% of those with MCS.UK FCS national registry
Variant classification changes the answer: in a Spanish registry study of 245 sequenced patients with severe hypertriglyceridemia, 20 had FCS with biallelic pathogenic or likely pathogenic variants, and FCS was excluded in 4 whose second variant was likely benign.Ariza 2025 Spanish registry
A lipemic sample can interfere with other laboratory measurements, a pediatric editorial notes, including coagulation tests in the case it discusses.Ariza 2022 pediatric editorial
Most severe hypertriglyceridemia is not FCS: among 563 patients with severe hypertriglyceridemia, 1.1% had biallelic rare variants and 46.3% had polygenic hypertriglyceridemia.Dron 2019 genetic study
The joint consensus notes that genetic testing is not routinely performed and that people from minority groups and economically disadvantaged backgrounds are less likely to be tested.NLA and ASPC consensus
Code E78.3 is not specific to FCS; Orphanet records its FCS entry (ORPHA:444490) as narrower than ICD-10 E78.3.Orphanet cross-references

Where to test

NIH Genetic Testing Registry: hyperlipoproteinemia, type I: The registry record that MedlinePlus Genetics links for this condition, listing tests submitted by laboratories. NIH does not independently verify submissions or endorse any laboratory.NIH GTR
Arrowhead Pharmaceuticals sponsored testing program (Ambry Genetics) (drugmaker-sponsored): Sponsored by Arrowhead Pharmaceuticals, which makes Redemplo (plozasiran). The Ambry Genetics program page describes a no-cost 5-gene panel (FCSNext: APOA5, APOC2, GPIHBP1, LMF1 and LPL), ordered only by a health care provider, for people aged 17 or older with a fasting triglyceride level above 600mg/dL in the past 12 months and no prior genetic testing for FCS. The page carries no date. An older Genome Medical page for the same sponsor still lists a 6-gene panel and a 750mg/dL threshold.Arrowhead sponsored testing page
Ionis FCS Testing Program (PreventionGenetics): closed (drugmaker-sponsored): Sponsored by Ionis Pharmaceuticals, which makes Tryngolza (olezarsen). The program page says it stopped accepting samples after October 31, 2026. It had covered US and Canadian residents with at least 2 consecutive fasting triglyceride levels above 880mg/dL (10mmol/L) and no secondary cause.Ionis FCS testing program page
Post-heparin LPL activity: GeneReviews says this assay is not routinely available and is generally only performed at selected specialist centers.GeneReviews
NIH's Genetic Testing Registry listed 0 tests for a search of “Familial chylomicronemia syndrome (FCS)” on November 13, 2026. NIH does not endorse or verify the labs it lists.

Family screening and referral

Who else in the family

GeneReviews, writing about LPL deficiency, says each sibling of an affected person has a 25% chance of being affected and a 50% chance of being heterozygous when both parents are heterozygous.GeneReviews
It considers it appropriate to evaluate at-risk siblings during infancy, with molecular testing for the familial LPL variants and a plasma triglyceride measurement.GeneReviews
It recommends a routine lipid panel for first-degree relatives, because heterozygotes are susceptible to hypertriglyceridemia that ranges from mild to severe.GeneReviews
It recommends molecular testing of both parents to confirm that each is heterozygous, and notes that a heterozygote's lipid results cannot be used to predict genetic status.GeneReviews
It says heterozygote testing should be considered for reproductive partners, particularly if consanguinity is likely or both partners share the same ancestry.GeneReviews
The UK registry authors call for timely genetic counseling and better regional genetic services where consanguineous unions are common.UK FCS national registry
NORD says genetic counseling is recommended for people with FCS and their family members.NORD report

Who to refer to

The joint NLA and ASPC consensus says a patient whose triglycerides stay at 1000mg/dL or more after secondary causes, lifestyle and fibrate therapy are addressed may benefit from referral to an expert in lipidology.NLA and ASPC consensus
It describes a multidisciplinary team of lipidologists, dietitians, primary care professionals, diabetologists, pancreatologists and, when cardiovascular risk is raised, cardiologists.NLA and ASPC consensus
It adds that women with persistent chylomicronemia need advice on contraception and pregnancy shared with their gynecologist or obstetrician.NLA and ASPC consensus
NORD says people with FCS typically receive care from endocrinologists or lipidologists and dietitians.NORD report
Respondents to the IN-FOCUS survey had seen a mean of 5 physicians from different specialties before their FCS diagnosis.IN-FOCUS patient survey
In England and Wales, many lipid centers have used a European FCS score of 8 or more as the threshold for NHS genetic testing since 2018, the UK registry reports.UK FCS national registry
The FDA label for Tryngolza (olezarsen), made by Ionis Pharmaceuticals, carries an indication to reduce triglycerides in adults with FCS as an adjunct to diet.Tryngolza label
The FDA label for Redemplo (plozasiran), made by Arrowhead Pharmaceuticals, carries the same indication for adults with FCS.Redemplo label
GeneReviews lists the FCS Foundation as a support organization for affected people and families.GeneReviews

Find a specialist by state

From the CMS NPI Registry, a public directory of US clinicians by registered specialty. A listing is not an endorsement and says nothing about experience with Familial chylomicronemia syndrome (FCS); patient organizations and academic centers can often name experienced clinicians.

ICD-10-CM codes for Familial chylomicronemia syndrome (FCS)

For orders, referrals and prior authorization. Each code is checked daily against NLM's ICD-10-CM service.

E78.3HyperchylomicronemiaCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

Once the diagnosis is confirmed

Familial chylomicronemia syndrome (FCS) drugs for prescribers2 prescribing guides, side by side: Redemplo, Tryngolza.Open trials: 2Screen a de-identified patient against every recruiting Familial chylomicronemia syndrome (FCS) study on ClinicalTrials.gov.Patient and family pageThe plain-language Familial chylomicronemia syndrome (FCS) page, with trials, treatments and help paying.

For the patient: why your doctor ordered this test

Plain language a patient can read or take home.

Your doctor ordered these tests because your triglycerides, a type of fat in the blood, have been very high more than once. One rare cause is familial chylomicronemia syndrome, often called FCS. In FCS the body cannot break down the fat particles that carry triglycerides after meals.

FCS can cause repeated attacks of pancreatitis, which is a painful swelling of the pancreas. It can also cause belly pain, small yellow bumps on the skin and blood that looks milky when it is drawn. Some people have signs as babies, and others are not diagnosed until they are adults.

Much more often, very high triglycerides come from a mix of common genes together with diabetes, weight, alcohol or certain medicines. To tell the difference, doctors or health care professionals may repeat your triglyceride test, review your history and medicines, and order a gene test that looks at 5 genes.

FCS is inherited when a child receives a changed gene from both parents. If it is found, your brothers, sisters and other close relatives may be offered a triglyceride test or a gene test.

Questions clinicians ask about Familial chylomicronemia syndrome (FCS) testing

Which combinations of findings should prompt testing for familial chylomicronemia syndrome (FCS)?

In published screening and biopsy studies, the highest yields came from history of chylomicronemia plus persistence despite control of secondary causes and conventional treatment (60% of 413 Caucasian patients with a history of chylomicronemia studied by Quebec and Houston authors, 65 of whom (15.7%) met criteria for persistent chylomicronemia), and from severe hypertriglyceridemia plus sequencing of the FCS genes (8.2% of 245 patients with severe hypertriglyceridemia sequenced in the Dyslipidemia Registry of the Spanish Atherosclerosis Society). Among patients already diagnosed, the most common combination began with severe hypertriglyceridemia, seen in 100% of 14 patients with genetically confirmed FCS (9 in a derivation group and 5 in a validation group) studied in Malaga and other Spanish centers. These figures describe study groups, not any one patient's chance of having familial chylomicronemia syndrome (FCS).

What triglyceride level should make me think of familial chylomicronemia syndrome?

A National Lipid Association expert review defines the severe hypertriglyceridemia of FCS as persistently 10mmol/L or more (885mg/dL or more), or 1000mg/dL or more depending on region, without secondary factors. GeneReviews lists untreated triglycerides above 2000mg/dL as a supportive finding for LPL deficiency. In the UK registry, all 74 patients with FCS were above 885mg/dL on at least 3 tests, and 99% had exceeded 1770mg/dL at least once.

How is FCS told apart from multifactorial chylomicronemia syndrome?

Only about 0.1% to 1% of patients with chylomicronemia have FCS, according to a joint NLA and ASPC consensus, so most have the multifactorial form. That consensus describes FCS as most often presenting in childhood, with normal or low body mass index, low LDL cholesterol and apolipoprotein B, persistent chylomicronemia and little or no response to fibrates or omega-3 fatty acids. In the UK registry, acute pancreatitis had occurred in 84% of patients with FCS against 60% with MCS, and symptoms began at a median of 15 against 34 years. Genetic testing for biallelic variants in LPL, APOC2, APOA5, GPIHBP1 or LMF1 confirms FCS.

What is the FCS score and how accurate is it?

The European FCS score, published by Moulin and colleagues in 2018, had 88% sensitivity and 85% specificity at a cut-off of 10 or more in 53 patients with FCS and 52 with MCS. Later validations reported 96% and 75% in the UK and 74.3% and 97.0% in Montreal. A North American score published in 2025 treats 45 or more as very likely FCS and 60 or more as definite. The companion data paper to the European score acknowledges medical writing paid for by Akcea Therapeutics, and a later Akcea and Ionis funded paper says the score arose from a sponsored meeting.

Which genes are tested for FCS, and what if the test is negative?

Testing covers 5 genes: LPL, APOC2, APOA5, GPIHBP1 and LMF1, and FCS requires biallelic pathogenic or likely pathogenic variants. Among 52 genotyped participants in the APPROACH trial, 41 had biallelic LPL variants. A Latin American Delphi panel notes that nearly 25% of patients with a clinical picture of FCS test negative, and suggests an LPL activity assay where available. GeneReviews says variants of uncertain significance neither establish nor rule out the diagnosis.

What is the ICD-10 code for familial chylomicronemia syndrome?

The ICD-10-CM code is E78.3, Hyperchylomicronemia, current in NLM's ICD-10-CM lookup checked November 13, 2026. Orphanet lists FCS as ORPHA:444490 and maps it to ICD-10 E78.3, noting that its entry is narrower than the code. The same lookup lists E78.1 as Pure hyperglyceridemia and K85.90 as acute pancreatitis without necrosis or infection, unspecified.

Sources

Lipoprotein Lipase Deficiency. GeneReviews, University of Washington, Seattle (Burnett JR, Hooper AJ, Hegele RA), via NCBI Bookshelf, 2026-07-23.
Familial chylomicronemia syndrome: An expert clinical review from the National Lipid Association. Journal of Clinical Lipidology 2025;19(3):382-403 (Javed F, Hegele RA, Garg A, Patni N, Gaudet D, Williams L et al; several authors report drugmaker consulting or grants, including from Ionis, Arrowhead and Akcea), via PubMed abstract, 2025-03-22.
Recognition and management of persistent chylomicronemia: A Joint Expert Clinical Consensus by the National Lipid Association and the American Society for Preventive Cardiology. Journal of Clinical Lipidology 2025;19(4):723-736 (Saadatagah S, Larouche M, Naderian M et al; no specific grant; several authors report Ionis or Arrowhead ties), via PubMed Central, 2025-03-28.
Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an "FCS score". Atherosclerosis 2018;275:265-272 (Moulin P, Dufour R, Averna M et al), via PubMed abstract; funding statement not seen. The companion paper (Data in Brief 2018;21:1334-1336, PMC6231039) acknowledges medical writing paid for by Akcea Therapeutics, 2018-06-18.
Development and validation of clinical criteria to identify familial chylomicronemia syndrome (FCS) in North America. Journal of Clinical Lipidology 2025;19(1):83-94 (Hegele RA, Ahmad Z, Ashraf A et al; 5 authors are from PHAR, Beverly Hills, CA), via PubMed abstract; funding and disclosures not seen, 2024-11-13.
Validation of the familial chylomicronaemia syndrome (FCS) score in an ethnically diverse cohort from UK FCS registry: Implications for diagnosis and differentiation from multifactorial chylomicronaemia syndrome (MCS). Atherosclerosis 2024;391:117476 (Bashir B, Kwok S, Wierzbicki AS et al; several authors report Akcea, Sobi or other drugmaker fees), via PubMed abstract, 2024-02-10.
Ethnic Diversity and Distinctive Features of Familial Versus Multifactorial Chylomicronemia Syndrome: Insights From the UK FCS National Registry. Arteriosclerosis, Thrombosis, and Vascular Biology 2024;44(11):2334-2346 (Bashir B, Downie P, Forrester N et al; the registry received an investigator-initiated grant from Akcea and Chiesi), via PubMed Central, 2024-09-05.
Validation of two familial chylomicronemia syndrome clinical diagnosis scores in a cohort of molecularly defined patients. Journal of Clinical Lipidology 2026;20(10):2128-2137 (Paquette M, Guay SP, Baass A; one author reports Akcea, Ionis, Arrowhead and other drugmaker grants or trial work), via PubMed abstract, 2026-08-07.
Comparison of different "familial chylomicronemia syndrome" clinical diagnosis scoring systems in patients with persistent chylomicronemia. Journal of Clinical Lipidology 2026;20(6):1133-1143 (Brisson D, Larouche M, Laflamme N et al; some authors report drugmaker grants or fees, including from Ionis and Arrowhead), via PubMed abstract, 2026-03-14.
Differentiating Familial Chylomicronemia Syndrome From Multifactorial Severe Hypertriglyceridemia by Clinical Profiles. Journal of the Endocrine Society 2019;3(12):2397-2410 (O'Dea LSL, MacDougall J, Alexander VJ et al; trials funded by Ionis Pharmaceuticals and Akcea Therapeutics, with Akcea and Ionis employees as authors), via PubMed Central, 2019-10-11.
Severe hypertriglyceridemia is primarily polygenic. Journal of Clinical Lipidology 2019;13(1):80-88 (Dron JS, Wang J, Cao H et al; Canadian Institutes of Health Research grant listed), via PubMed abstract, 2018-10-24.
The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study. Journal of Clinical Lipidology 2018;12(4):898-907.e2 (Davidson M, Stevenson M, Hsieh A et al; Akcea Therapeutics employees among the authors), via PubMed abstract; funding statement not seen, 2018-04-26.
Characterizing familial chylomicronemia syndrome: Baseline data of the APPROACH study. Journal of Clinical Lipidology 2018;12(5):1234-1243.e5 (Blom DJ, O'Dea L, Digenio A et al; Akcea and Ionis employees among the authors; APPROACH was funded by Ionis Pharmaceuticals and Akcea Therapeutics per O'Dea 2019), via PubMed abstract, 2018-05-31.
Clinical and biochemical features of different molecular etiologies of familial chylomicronemia. Journal of Clinical Lipidology 2018;12(4):920-927.e4 (Hegele RA, Berberich AJ, Ban MR et al; Akcea and Ionis employees among the authors; participants came from the Ionis and Akcea funded APPROACH trial; Canadian Institutes of Health Research grant listed), via PubMed abstract, 2018-04-04.
Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia. Journal of Internal Medicine 2020;287(4):340-348 (Baass A, Paquette M, Bernard S, Hegele RA), via PubMed abstract; funding and disclosures not seen, 2020-01-08.
Chylomicronemia: Differences between familial chylomicronemia syndrome and multifactorial chylomicronemia. Atherosclerosis 2019;283:137-142 (Paquette M, Bernard S, Hegele RA, Baass A), via PubMed abstract; funding and disclosures not seen, 2018-12-28.
A multi-society Delphi consensus statement on the diagnosis of familial chylomicronemia syndrome. Archives of Endocrinology and Metabolism 2025;69(5):e250071 (Aguilar-Salinas CA, Alonso R, Berg G et al; several authors report drugmaker honoraria, including from PTC Therapeutics; no funding statement seen), via PubMed Central, 2025-09-30.
Familial chylomicronemia syndrome in children: a diagnosis challenge. Translational Pediatrics 2022;11(11):1743-1747 (Ariza MJ, Valdivielso P; commissioned editorial, no funding, both authors report past Akcea fees), via PubMed Central, 2022-11.
Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: Novel cases of familial chylomicronemia syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. Genetics in Medicine 2025;27(5):101365 (Ariza MJ, Coca-Prieto I, Rioja J et al; some authors report Akcea, Sobi or other drugmaker fees or grants), via PubMed abstract, 2025-01-24.
Role of lipoprotein lipase activity measurement in the diagnosis of familial chylomicronemia syndrome. Journal of Clinical Lipidology 2023;17(2):272-280 (Rioja J, Ariza MJ, Benítez-Toledo MJ et al; no competing interests declared), via PubMed abstract, 2023-01-26.
Brief communication: Strong concordance of the North American Familial Chylomicronemia Syndrome Score with a positive genetic diagnosis in patients from the Balance study. Journal of Clinical Lipidology 2025;19(5):1451-1456 (Brown AS, Moulin P, Dibble A et al; Ionis employees among the authors; patients came from the Balance trial of olezarsen), via PubMed abstract; funding statement not seen, 2025-07-23.
Application of the North American Familial Chylomicronemia Syndrome Score (NAFCS Score) in monogenic hypertriglyceridemia patients: A single-center Turkish cohort study. Journal of Clinical Lipidology 2026;20(2):310-316 (Simsir IY, Belen O, Ciftci P et al, Ege University, Izmir), via PubMed abstract; funding and disclosures not seen, 2025-11-08.
Course of Pregnancies and Occurrence of Acute Pancreatitis in Women With Chylomicronemia. Journal of Clinical Endocrinology and Metabolism 2026;111(2):e455-e461 (Larouche M, Bergeron J, Brisson D et al; the paper states no funding; several authors report grants or fees from drugmakers including Ionis, Arrowhead and Akcea), full text in PubMed Central (PMC12819854), 2026-01-21.
Familial lipoprotein lipase deficiency: MedlinePlus Genetics. National Library of Medicine, 2015-02-01.
Familial Chylomicronemia Syndrome - Symptoms, Causes, Treatment | NORD. National Organization for Rare Disorders, 2025-02-03.
Familial chylomicronemia syndrome, ORPHA:444490, rare disease cross-referencing (Orphadata API). Orphanet, INSERM, via Orphadata, CC BY 4.0, 2026-06-23.
Identify Genetic Etiologies in Patients w/ Severe Hypertriglyceridemia. Ambry Genetics, with Arrowhead Pharmaceuticals, 2026-11-13.
Ionis Familial Chylomicronemia Syndrome (FCS) Testing Program | PreventionGenetics. PreventionGenetics, sponsored by Ionis Pharmaceuticals, 2026-11-13.
Tryngolza (olezarsen sodium) [Ionis Pharmaceuticals, Inc.] (prescribing information). Ionis Pharmaceuticals, via openFDA, 2026-07-03.
Redemplo (plozasiran) [Arrowhead Pharmaceuticals, Inc.] (prescribing information). Arrowhead Pharmaceuticals, via openFDA, 2026-08-25.
NIH Genetic Testing Registry tests for hyperlipoproteinemia, type I, MedGen concept C0023817 (40 tests listed in NCBI E-utilities on November 13, 2026). National Center for Biotechnology Information, NIH, 2026-11-13.
ICD-10-CM search results for "E78.3" (Clinical Table Search Service). National Library of Medicine, 2026-11-13.

A reference for licensed professionals, checked against its sources on November 13, 2026. It summarizes what the cited guidance says and does not tell anyone how to diagnose or treat a specific patient. Guidelines change; the current guideline and the treating clinician's judgment govern. Trial Friend is an independent information service, not a medical provider.