ESPE Yearbook of Paediatric Endocrinology

Journal of Clinical Endocrinology and Metabolism. 2018; 103(6): 2403–7.
URL: http://www.ncbi.nlm.nih.gov/pubmed/29659879

Summary: Orlistat therapy reduced serum triglycerides by 50–60% in two children with Type 1 hyperlipoproteinemia (T1HLP) in a randomized, open-label, crossover trial with four periods and two sequences. The treatment was safe and is suggested as first-line therapy in conjunction with an extremely low-fat diet and fat-soluble vitamin supplementation.

Comment: T1HLP, also known as familial chylomicronemia syndrome, is a rare, autosomal recessive condition characterized by extreme hypertriglyceridemia due to a deficiency in the enzyme lipoprotein lipase (LPL) or other proteins necessary for proper LPL function, such as LMF1, APOC2, APOA5 and GPIHBP1. Triglyceride (TG) levels may range from 1,500 to 15,000 mg/dl, and result in eruptive or tuberous xanthomas, recurrent pancreatitis, lipemia retinalis and hepatosplenomegaly. In 2012, an adeno-associated virus gene therapy (alipogene tiparvovec) was the first gene therapy approved in Europe for LPL deficiency. This treatment is administered by multiple intramuscular injections (>40) in the legs given at a single visit, under spinal anesthesia. As patients developed antibodies to the capsid proteins, the lowering effect of TGs was transient and this treatment was withdrawn from the market in 2017. The only currently available effective therapy is an extremely low-fat diet with 10% to 15% of the total energy as fat.

Orlistat is a gastric and pancreatic lipase inhibitor that can lower dietary fat absorption by 30%, and therefore, may reduce serum TG levels in patients with T1HLP by decreasing the substrate available for chylomicron formation. Two children participated in an alternating, repeated crossover trial with four periods and two sequences (‘orlistat’ and ‘off’ for 3 months each). Orlistat therapy reduced mean fasting serum TGs by 50%, without any serious adverse effects.

Longer-term clinical trials with a larger number of patients are warranted to determine the efficacy and safety of orlistat with prolonged use in patients with T1HLP for preventing acute pancreatitis