Abetalipoproteinaemia

Abetalipoproteinaemia is a rare genetic disorder caused by impaired transport of intestinal and hepatic lipids that typically presents in the first few months of life with symptoms of faltering growth and steatorrhoea.

Diagnosis is often missed due to vague symptoms more common to diseases such as viral gastroenteritis or child abuse sequelae.

If untreated, the disorder is progressive. Deficiency of fat-soluble vitamins such as A, E, D, and K can lead to clinical symptoms and neurological deterioration.

When treated early with high doses of vitamin E, sequelae such as retinal degeneration or ataxia may be prevented.

Nutritional repletion, including a low-fat diet and ingestion of fat-soluble vitamins, is essential in management.

Abetalipoproteinaemia is a rare, inherited, autosomal-recessive disorder resulting from microsomal triglyceride transfer protein deficiency in the liver and small intestine.[1]Shapiro MD, Feingold KR. Monogenic disorders causing hypobetalipoproteinemia. In: Feingold KR, Anawalt B, Boyce A, et al. eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000–2021. https://www.ncbi.nlm.nih.gov/books/NBK326744 [2]Lee J, Hegele RA. Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management. J Inherit Metab Dis. 2014 May;37(3):333-9. http://www.ncbi.nlm.nih.gov/pubmed/24288038?tool=bestpractice.com [3]Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014 Jun;25(3):161-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465983 http://www.ncbi.nlm.nih.gov/pubmed/24751931?tool=bestpractice.com Fat transport is disrupted, causing symptoms of fat malabsorption (i.e., steatorrhoea, diarrhoea, abdominal distension) and eventual wasting, which often present by infancy or childhood.[2]Lee J, Hegele RA. Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management. J Inherit Metab Dis. 2014 May;37(3):333-9. http://www.ncbi.nlm.nih.gov/pubmed/24288038?tool=bestpractice.com [4]Bredefeld C, Peretti N, Hussain MM, et al. New classification and management of abetalipoproteinemia and related disorders. Gastroenterology. 2021 May;160(6):1912-6. https://www.doi.org/10.1053/j.gastro.2020.11.040 http://www.ncbi.nlm.nih.gov/pubmed/33275938?tool=bestpractice.com Fats, cholesterol, and fat-soluble vitamins such as A, D, E, and K are poorly absorbed, leading to dietary deficiency.[1]Shapiro MD, Feingold KR. Monogenic disorders causing hypobetalipoproteinemia. In: Feingold KR, Anawalt B, Boyce A, et al. eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000–2021. https://www.ncbi.nlm.nih.gov/books/NBK326744 [2]Lee J, Hegele RA. Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management. J Inherit Metab Dis. 2014 May;37(3):333-9. http://www.ncbi.nlm.nih.gov/pubmed/24288038?tool=bestpractice.com [5]Burnett JR, Hooper AJ. Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. Free Radic Biol Med. 2015 Jun 16;88(pt a):59-62. http://www.ncbi.nlm.nih.gov/pubmed/26086616?tool=bestpractice.com [6]Zamel R, Khan R, Pollex RL, et al. Abetalipoproteinemia: two case reports and literature review. Orphanet J Rare Dis. 2008 Jul 8;3:19. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2467409/?tool=pubmed http://www.ncbi.nlm.nih.gov/pubmed/18611256?tool=bestpractice.com  If discovered early and treated, nutrition may be improved and sequelae prevented. If untreated, clinical findings of vitamin E deficiency result from degeneration of the spinocerebellar and dorsal columns tracts. Irreversible effects include ataxia, peripheral neuropathy, and retinal degeneration.[6]Zamel R, Khan R, Pollex RL, et al. Abetalipoproteinemia: two case reports and literature review. Orphanet J Rare Dis. 2008 Jul 8;3:19. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2467409/?tool=pubmed http://www.ncbi.nlm.nih.gov/pubmed/18611256?tool=bestpractice.com