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A severe, familial hypobetalipoproteinemia characterized by permanently low levels (below the 5th percentile) of apolipoprotein B and LDL cholesterol, and by growth delay, malabsorption, hepatomegaly, and neurological and neuromuscular manifestations.
ORPHA:14Classification level: Disorder
It is very rare, with an estimated prevalence of less than 1/1,000,000.
Abetalipoproteinemia manifests during the first year of life or in young childhood. It is often associated with growth delay, hepatomegaly with steatosis, diarrhea with steatorrhea, and fat malabsorption. Spastic ataxia, atypical retinitis pigmentosa, acanthocytosis, a low level of liposoluble vitamins, and major cytolysis and even cirrhosis can occur.
Abetalipoproteinemia is a result of mutations of two alleles of the MTTP gene (MTP; 4q24). Other severe early familial hypobetalipoproteinemias are inherited in a codominant manner and are a result of mutations of two alleles of the APOB gene (2p24-p23).
Diagnosis is based on lipid analysis, after 12 hours of fasting, carried out on the patient and their parents to measure serum levels of LDL (<0.10g/L), triglycerides (<0.20 g/L), and apolipoprotein B (<0.10g/L). Identification of steatorrhea and truncated apolipoprotein B after oral lipid intake, measurement of liposoluble vitamins (A, E, K), testing for acanthocytosis (on blood smears), complete neurological examination, hepatic ultrasound and eye examination can also be carried out. Identification of mutations of the MTTP or APOB genes confirms the diagnosis.
Differential diagnoses include metabolic diseases with hepatic overload, with steatosis and/or hepatomegaly, atypical diseases of the central and peripheral nervous system, and secondary causes of hypocholesterolemia (iatrogenic or systemic).
Prenatal diagnosis is possible when the causal mutations in both parents are known.
Abetalipoproteinemia is inherited in a recessive manner.
Management and treatment
Management should be undertaken in specialized centers.
The prognosis is severe, with a significantly reduced life expectancy.