Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management.

Abetalipoproteinemia (ABL; OMIM 200100) and homozygous hypobetalipoproteinemia (HHBL; OMIM 107730) are rare diseases characterized by hypocholesterolemia and malabsorption of lipid-soluble vitamins leading to retinal degeneration, neuropathy and coagulopathy. Hepatic steatosis is also common. The root cause of both disorders is improper packaging and secretion of apolipoprotein (apo) B-containing lipoprotein particles due to mutations either in both alleles of the MTP (alias MTTP) gene encoding microsomal triglyceride transfer protein (MTP) or both alleles of the APOB gene itself in the case of ABL and HHBL, respectively. Clinical diagnosis is based on signs and symptoms, acanthocytosis on blood smear, and virtually absent apo B-containing lipoproteins, including chylomicrons, very low density lipoprotein and low density lipoprotein. Obligate heterozygote parents of ABL patients usually have normal lipids consistent with autosomal recessive inheritance, while heterozygous parents of HHBL patients typically have half normal levels of apo B-containing lipoproteins consistent with autosomal co-dominant inheritance. Definitive diagnosis involves sequencing the MTP and APOB genes, for which >30 and >60 mutations have been described for ABL and HHBL, respectively. Follow-up includes monitoring for ophthalmologic, neurologic, hematologic, and hepatic complications, as well as compliance with treatment. Investigations include lipid profile, serum transaminases, markers for lipid-soluble vitamins, and periodic instrumental assessment of ocular and neurological function. Mainstays of treatment include adherence to a low-fat diet, and supplementation with essential fatty acids and high oral doses of fat soluble vitamins. Prognosis is variable, but early diagnosis and strict adherence to treatment can recover normal neurological function and halt disease progression.