Familial Hypertriglyceridemia

Excerpt

Familial hypertriglyceridemia (FHTG), also known as type IV familial dyslipidemia, is a genetic disorder characterized by hepatic overproduction of very low-density lipoproteins (VLDL), leading to elevated serum levels of triglycerides and VLDL. This condition typically follows an autosomal dominant inheritance pattern, giving affected individuals a 50% chance of passing the disorder to their offspring. Recent evidence suggests a polygenic basis, with multiple genetic variants contributing to the phenotype.

Type IV familial dyslipidemia falls within the Fredrickson classification system of lipid disorders, also known as the World Health Organization (WHO) classification of hyperlipidemias. Developed by American physician Donald Fredrickson in the 1960s, this system categorizes hyperlipidemias into 5 major types based on the elevation of different lipoproteins.

Clinically, FHTG presents with mild-to-moderate elevations in serum triglyceride concentrations, often accompanied by comorbidities such as obesity, hyperglycemia, and hypertension. Individuals with this disorder frequently have heterozygous inactivating mutations in the lipoprotein lipase (LPL) gene, which alone can significantly raise triglyceride levels. In combination with medications or coexisting conditions, these mutations can further increase serum triglyceride levels and cause acute pancreatitis.

Early identification and intervention are crucial, as individuals with FHTG may be asymptomatic until severe complications arise. Recognizing clinical signs such as xanthomas, hepatomegaly, and lipemia retinalis, along with obtaining a thorough family medical history, aids in the timely diagnosis of this condition. Effective management of FHTG requires a multifaceted approach, integrating lifestyle modifications and pharmacological therapies.