IllnessHypertriglycerolaemia, differential diagnosis

NGS +

[Sanger]

Hypertriglyceridemia (HTG) is usually multifactorial and results from low-effect variants (single nucleotide polymorphisms) in genes such as APOA5, LPL, APOB and GCKR, with more than 20% of susceptibility due to common and rare variants. Chylomicronemia syndrome is defined by abdominal pain, eruptive xanthomas, plasma triglyceride concentrations greater than 2000 mg/dL and fasting lipemia. Heterozygous relatives of cases with homozygous familial chylomicronemia carry loss-of-function mutations in genes such as LPL, APOC2, APOA5, LMF1 as well as GPIHBP and are asymptomatic. Although they have near-normal lipids, they can develop severe HTG when exogenous factors such as alcohol, oral estrogen treatment, obesity and/or pregnancy are involved (risk for acute pancreatitis). Susceptibility to environmental factors is common; typical example is a child with mild LDL-cholesterol elevation who develops an increase in triglycerides and non-HDL cholesterol during adolescence. HTG is exacerbated by obesity as well as alcohol consumption and oral estrogens. Because insulin resistance and T2D are more common in adolescence, gene-environment interaction leads to mixed dyslipidemia with variable elevations of TG and cholesterol. Because of the complex multifactorial genesis, a negative molecular genetic result cannot exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK395574/

• Alias: Hyperlipidemia
• Alias: Hypertriglyceridämie
• Allelic: Diabetes mellitus, noninsulin-dependent (LIPC)
• Apolipoprotein C-III deficiency (APOC3)
• Combined hyperlipidemia, familia (LPL)
• Hepatic lipase deficiency (LIPC)
• High density lipoprotein cholesterol level QTL 11 (LPL)
• High density lipoprotein cholesterol level QTL 12 (LIPC)
• Hyperchylomicronemia, late-onset (APOA5)
• Hyperlipidemia, familial combined, susceptibility to (USF1)
• Hyperlipoproteinemia, type 1D (GPIHBP1)
• Hyperlipoproteinemia, type Ib (APOC2)
• Hypertriglyceridemia, susceptibility to (APOA5)
• Hypertriglyceridemia, transient infantile (GPD1)
• Lipase deficiency, combined (LMF1)
• Lipodystrophy, familial partial, type 6 (LIPE)
• Lipoprotein lipase deficiency (LPL)
• Monogenic dominant hypertriglyceridemia associated with (CREB3L3)
• Plasma triglyceride level QTL, low (ANGPTL4)