Cardiology > Lipoproteins / Lipoprotein Lipase Deficiency    

Background 

Lipoproteins are complexes of lipids and proteins that transport triglycerides and cholesterol through the bloodstream. Lipoprotein lipase (LPL) is a critical enzyme that hydrolyzes triglycerides from circulating chylomicrons and very low-density lipoproteins (VLDL), allowing free fatty acids to be taken up by tissues. 
Lipoprotein lipase deficiency is a rare autosomal recessive disorder characterized by absent or markedly reduced LPL activity, leading to accumulation of chylomicrons and severe hypertriglyceridemia, often presenting in childhood with eruptive xanthomas and risk of pancreatitis. 

II) Classification/Types

By Lipoprotein Class: 

• • Chylomicrons: Carry dietary triglycerides from the intestine to peripheral tissues 

• • VLDL: Carry endogenous triglycerides from the liver 

• • LDL (low-density): Delivers cholesterol to peripheral tissues 

• • HDL (high-density): Removes cholesterol from tissues for reverse transport 

By Genetic Defect: 

• • Type I Hyperlipoproteinemia (Familial Chylomicronemia Syndrome): LPL gene mutations or ApoC-II deficiency 

• • Multifactorial Chylomicronemia: Secondary causes with polygenic background and partial LPL deficiency 

 
Pathophysiology 

In LPL deficiency, impaired hydrolysis of triglyceride-rich lipoproteins (especially chylomicrons) results in massive accumulation of triglycerides in plasma. This leads to lipemic serum, reduced fatty acid uptake in tissues, and potential end-organ damage. The lack of functional LPL prevents normal lipid clearance, leading to severe fasting hypertriglyceridemia (>1,000–2,000 mg/dL). Pancreatic capillaries may become clogged with chylomicrons, triggering pancreatitis. 

Epidemiology 

• • Extremely rare: Incidence of 1 in 1,000,000 

• • Often presents in infancy or early childhood 

• • Equal male-to-female ratio 

• • More prevalent in genetically isolated populations (e.g., Quebec, Canada) 

• • Multifactorial forms more common in adults with metabolic syndrome 

Etiology 

I) Causes

• • Genetic mutations in: 

• • LPL (most common) 

• • ApoC-II (activator of LPL) 

• • GPIHBP1, LMF1, APOA5 (less common) 

II) Risk Factors

• • Positive family history 

• • Consanguinity 

• • Secondary contributors: 

• • Uncontrolled diabetes 

• • Alcohol use 

• • Pregnancy 

• • Estrogen therapy 

• • Obesity and metabolic syndrome 

Clinical Presentation 

I) History (Symptoms)

• • Recurrent abdominal pain (especially post-fatty meals) 

• • Episodes of acute pancreatitis 

• • Failure to thrive or irritability in infants 

• • Fatigue, nausea 

• • Visual changes (lipemia retinalis) 

II) Physical Exam (Signs)

• • Eruptive xanthomas: Yellowish papules on back, buttocks, or extensor surfaces 

• • Hepatosplenomegaly 

• • Lipemia retinalis: Cream-colored retinal vessels (TG >2000 mg/dL) 

• • Pancreatic tenderness in acute episodes 

• • Milky appearance of plasma (lipemic serum) 

Differential Diagnosis (DDx) 

• • Familial combined hyperlipidemia 

• • Familial dysbetalipoproteinemia 

• • Secondary hypertriglyceridemia (e.g., diabetes, hypothyroidism) 

• • Gaucher disease 

• • Tangier disease 

• • Insulin resistance syndromes 

Diagnostic Tests 

Initial Work-Up 

• • Fasting lipid panel: TG >1,000–2,000 mg/dL; elevated chylomicrons 

• • Serum appearance: Milky or lipemic 

• • Pancreatic enzymes: Amylase, lipase (if abdominal pain) 

• • Genetic testing: Confirmatory (LPL, ApoC-II mutations) 

• • ApoC-II levels: Distinguish from ApoC-II deficiency 

• • LPL activity assay: Functional enzyme test (specialized) 

Advanced Testing 

• • Ophthalmologic exam: Lipemia retinalis 

• • Abdominal imaging (US/CT): Assess for pancreatitis or hepatosplenomegaly 

Treatment 

I) Initial Approach

• • Immediate goal: Prevent or treat pancreatitis 

• • Dietary fat restriction: <15% of total daily calories from fat 

• • Avoid long-chain triglycerides (LCTs) 

• • Hospitalization in case of pancreatitis 

• • Avoid alcohol and medications that increase triglycerides 

II) Medications

*Alipogene tiparvovec was the first gene therapy approved for LPL deficiency but is no longer marketed. 

Patient Education, Screening, Vaccines 

Education 

• • Fat-free diet for life (restrict animal fats, oils, nuts, fried foods) 

• • Use medium-chain triglycerides (MCTs) as energy source 

• • Recognize signs of pancreatitis early 

• • Genetic counseling for families 

• • Importance of lifelong adherence 

Screening 

• • Lipid panels for siblings and offspring 

• • Family history assessment 

• • Genetic testing in suspected cases 

Vaccinations 

• • Influenza and pneumococcal vaccines (especially if history of pancreatitis) 

• • Hepatitis B vaccination (if frequent hospitalizations or parenteral nutrition) 

Consults/Referrals 

• • Genetics: Confirm diagnosis, counseling 

• • Nutritionist: Specialized low-fat dietary planning 

• • Pediatrics or Metabolic Specialist: For children with failure to thrive or syndromic features 

• • Gastroenterology: For recurrent pancreatitis 

• • Ophthalmology: Lipemia retinalis evaluation 

Follow-Up 

Short-Term 

• • Monitor triglyceride levels every 1–3 months 

• • Monitor growth in children 

• • Monitor for abdominal pain or signs of pancreatitis 

Long-Term 

• • Lifelong fat-restricted diet adherence 

• • Monitor liver function, fat-soluble vitamin levels (A, D, E, K) 

• • Routine genetic counseling in families 

• • Periodic imaging if recurrent pancreatitis 

Prognosis 

• • Good if triglyceride levels are tightly controlled with dietary therapy 

• • Poor if untreated, with high risk of life-threatening pancreatitis 

• • Growth and development may be affected if diet is not optimized in children 

• • Gene therapy holds potential for future treatment in monogenic cases