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Alagille Syndrome (ALGS)

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Nutrition

Alagille syndrome (ALGS) is a multisystem inherited disease that typically manifests as cholestasis and can progress to end-stage liver disease and death.1 The restricted flow of bile to the small intestine in ALGS can make it difficult to digest fats and absorb fat-soluble vitamins (A, D, E, and K). This can lead to malnutrition and complications including bone issues, development problems, delayed puberty, and failure to thrive. Vitamin levels should be checked on a regular basis, and fat-soluble vitamins and other nutrients should be supplemented as necessary.2

Children with ALGS frequently have growth failure, delayed puberty, and malnutrition. Children with ALGS experience more growth failure than children with other chronic liver disorders like biliary atresia. Growth failure in ALGS may occur due to malabsorption of fat from the liver and pancreas, inadequate intake of nutrients or calories, or defects in the Jagged1 gene.3 

For children with ALGS, a proper diet is essential to prevent and treat development failure and nutritional deficiencies. A registered dietitian should evaluate affected children to determine their growth and nutritional status and give specific dietary recommendations. A nasogastric tube or a gastrostomy tube may be needed to promote the nutrition and growth of children who cannot consume enough calories or have poor growth.3

Children with ALGS who have undergone liver transplants do not completely catch up in growth compared to children with other liver illnesses, suggesting that the primary gene deficiency in Jagged1 may be responsible for their poor growth. ALGS can also affect organ systems including the heart and kidneys, causing growth problems. It is critical for children with ALGS to consume enough calories and achieve adequate vitamin levels in their blood.3 

Alagille Syndrome Diet

Diets heavy in carbohydrates and medium-chain triglycerides are better absorbed in patients with ALGS. Drip feeds via a nasogastric tube or gastrostomy may be considered in patients with inadequate weight gain and increased caloric needs due to malabsorption, cholestasis, or heart dysfunction. If not properly supplemented, an essential fatty acid deficiency may occur. Fat-soluble vitamins must be supplemented.4 

Fat-Soluble Vitamins

In ALGS, reduced bile acid flow to the small intestine hampers the digestion of fats and the absorption of fat-soluble vitamins A, D, E, and K. This may result in malnutrition and growth deficiencies. Thus, patients may need oral supplementation with vitamins A, D, E, and K to compensate for their deficiency.5 It is recommended that supplements are given individually and not as multivitamin preparations based on the levels of individual vitamins in the blood, which should be measured periodically (2 to 3 times per year) to allow for dose adjustment. Cholestasis-specific vitamin formulations are available for fat-soluble vitamin supplementation.6 

Vitamin K

Vitamin K is necessary for bone health and blood clotting. Vitamin K insufficiency causes children to bruise and bleed more readily. Cabbage, cauliflower, spinach, and other green leafy vegetables, as well as grains, soybeans, and other vegetables, contain vitamin K. If oral vitamin K fails to restore blood clotting times, intramuscular vitamin K injections may be required.3 All babies with jaundice lasting longer than 14 days are advised to undergo medical evaluation.7 A formulation of vitamin K compound solubilized in active constituent of mixed micelles containing glycocholate and lecithin efficiently corrects vitamin K deficiency. The ampoule solution is clear to slightly opalescent, pale yellow in colour.8

Vitamin E

Vitamin E has antioxidant properties that prevent the oxidation of vitamins A and C and protect cellular membranes from oxidative damage. It is needed for a healthy nervous system and the development of coordination. Its deficiency results in neurological deficits such as poor nerve conduction, incoordination, and developmental delays. Deficiency can cause decreased reflexes, weakness, wide gait (walking with the legs far apart), and hemolytic anemia. Vitamin E deficiency can still occur in children with cholestasis even after receiving high doses of vitamin E (either alpha tocopherol or alpha tocopherol acetate). The preferred form of vitamin E replacement therapy in patients with cholestasis is the liquid form, tocopherol polyethylene glycol 1000 succinate (TPGS), which is directly absorbed from the intestine without the need for bile acids. TPGS also improves vitamin D absorption. Vitamin E levels must be checked on a regular basis.3,9  

Vitamin D

Optimal levels of vitamin D are required for bone health. With vitamin D deficiency, children’s bones can turn weak, brittle, and soft, and rickets can occur. Vitamin D can be produced by the body when exposed to sunlight.3 The status of vitamin D is determined by measuring serum levels of 25-hydroxy cholecalciferol, which is a metabolite of vitamin D formed in the liver.10 

Vitamin A

Normal vision, cellular differentiation, reproduction, growth, and immunological function all require vitamin A. Vitamin A is predominantly found in animal-based foods such as liver, dairy products like whole milk, cheese, and butter, and fish like tuna and sardines. Growth retardation, increased susceptibility to infection, and night blindness are all clinical features of vitamin A deficiency. Over supplementation of vitamin A can be harmful to the liver, therefore those with ALGS should be cautious. To minimize toxicity, blood levels must be carefully monitored.3 The most convenient way to assess vitamin A status is to measure serum retinol levels. Because excessive levels of vitamin A can lead to fatal liver toxicity, it is important to regularly monitor levels in children receiving supplementation.10

Other Supplements

If laboratory results reveal a deficiency in zinc, selenium, calcium, phosphorus, or magnesium, supplements should be provided. Zinc is a necessary cofactor for a number of enzymes involved in immunological function, tissue repair, appropriate growth, and development. Growth retardation, skin rashes, diarrhea, delayed sexual maturation,  and appetite loss are all symptoms of zinc deficiency.3 

References 

  1. Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2018;67(2):148-156. doi:10.1097/MPG.0000000000001958
  2. Eating, diet, & nutrition for Alagille syndrome. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Accessed March 9, 2022.
  3. Alagille syndrome. Children’s Hospital of Philadelphia. Accessed March 9, 2022.
  4. Scheimann A. Alagille syndrome treatment & management. Medscape. Updated October 1, 2021. Accessed March 9, 2022.
  5. Yang CH, Perumpail BJ, Yoo ER, Ahmed A, Kerner JA Jr. Nutritional needs and support for children with chronic liver disease. Nutrients. 2017;9(10):1127. doi:10.3390/nu9101127
  6. Ayoub MD, Kamath BM. Alagille syndrome: diagnostic challenges and advances in management. Diagnostics (Basel). 2020;10(11):907. doi:10.3390/diagnostics10110907
  7. Mahadevan SBK, Beath SV, McKiernan PJ, Kelly DA. The vitamin K debacle and infants with cholestatic liver disease. Arch Dis Child. 1999;81(3):281. doi:10.1136/adc.81.3.i278
  8. Konakion MM paediatric 2 mg/0.2 ml. Electronic Medicines Compendium (emc). Updated February 16, 2022. Accessed March 9, 2022..
  9. Tocophersolan. PubChem. Accessed March 9, 2022.
  10. Socha P. Nutritional management of cholestatic syndromes in childhood. Ann Nestle Eng. 2008;66:137-147. doi:10.1159/000147411

Reviewed by Debjyoti Talukdar, MD, on 3/10/2022.

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