Abetalipoproteinemia

Abetalipoproteinaemia is a rare autosomal recessive disorder of lipoprotein assembly due to mutations in the microsomal triglyceride transfer protein (MTTP) gene, causing absence of apolipoprotein B containing lipoproteins (chylomicrons, VLDL, LDL).

Prevalence is under 1 in 1 million; consanguinity common.

Consequences: severe fat malabsorption, deficiency of fat soluble vitamins (A, E, K, D), acanthocytosis, hypocholesterolaemia (total cholesterol under 50 mg/dL), very low triglycerides, absent apoB.

• Infancy: steatorrhoea, diarrhoea, vomiting, abdominal distension, failure to thrive.
• Neurological (progressive without treatment, after age 10): areflexia, loss of proprioception and vibration sense, ataxia, dysarthria, tremor, muscle weakness, intellectual decline.
• Ocular: night blindness, pigmentary retinopathy, visual loss, ophthalmoplegia.
• Acanthocytes on blood film, bleeding tendency (vitamin K deficiency), hepatomegaly.

• Lipid profile: very low or undetectable total cholesterol, LDL cholesterol, triglycerides; absent apolipoprotein B on assay; failure of triglyceride rise after a fat meal.
• Blood film: acanthocytosis (50 to 90% of red cells), low ESR.
• Vitamin levels: low vitamin E (under 0.5 mg/L, ratio to lipids), A, K (raised INR), 25 hydroxyvitamin D.
• Intestinal biopsy: lipid laden enterocytes with normal villi.
• Liver ultrasound/elastography, liver enzymes.
• Genetic testing for MTTP and APOB.
• Ophthalmology (retinal examination, electroretinography), neurological examination, nerve conduction.

• Dietary fat restriction (under 15 to 20% of calories, 30 to 40 g/day) to reduce steatorrhoea, and medium chain triglyceride supplementation; adequate essential fatty acids (linoleic acid, 1 to 2% of calories via safflower oil).
• Lifelong high dose fat soluble vitamin supplementation:
  • Vitamin E 100 to 300 mg/kg/day (up to 5 to 10 g/day in adults) in divided doses, monitoring serum levels.
  • Vitamin A 100 to 400 units/kg/day (10,000 to 25,000 IU daily), with caution in liver disease.
  • Vitamin K 5 to 10 mg orally weekly or 1 to 2 mg daily.
  • Vitamin D 1000 to 4000 IU daily.
• Early treatment prevents or halts neurological and retinal degeneration; established damage is partially reversible.
• Monitor lipids, vitamin levels, liver function, INR, neurological and ophthalmic examination every 6 to 12 months.
• Manage hepatic steatosis (weight, avoid alcohol), screen for fibrosis.
• Genetic counselling for family. Lomitapide is contraindicated.
• Nutritional rehabilitation, growth monitoring, and parenteral nutrition for severe malnutrition.