• What is tyrosinemia?

Tyrosinemia is an inborn error or metabolism i.e., a genetic error in the breakdown of an  amino acid called tyrosine. Due to the error in breakdown, tyrosine and certain by-products accumulate in the body and cause the various disease manifestations.

  • What is the defect in tyrosinemia?

Tyrosinemia can be due to a defect in various enzymes involved in tyrosine breakdown. However, the type called tyrosinemia type 1 or hepatorenal tyrosinemia is the only one that affects the liver.
It is caused by the deficiency of an enzyme called fumerylacetoacetate hydrolase (FAH). This defect is genetic and is inherited from parents; hence may run in families.

  • How common is this disease?

It is a rare disorder, with an estimated prevalence of 1:1,00,000 in the world. The prevalence in India is not known, and perhaps goes undiagnosed.

  • What are the manifestations of this disease?

This disease usually presents in infancy i.e. in children less than 1 year of age and even as early as the newborn period, but can affect adults also.
The disease mainly affects liver, nerves and kidneys. It is many times precipitated by events like fever or some other infection.
Most commonly, the children present with liver problems and acute liver failure like

  1. fever,
  2.  irritability
  3. vomiting,
  4. jaundice,
  5. bleeding from skin leading to bluish spots on the skin,
  6. black stool(malena).
  7.  The child may have a peculiar odour of a boiled cabbage.

Doctor examining the child will find an enlarged liver, fluid in abdomen, low sugars and increased liver function tests specially liver enzymes.
Often after the acute episode is managed, certain problems persists like low weight gain, poor growth of the child, liver may remain enlarged and there may be some tests of liver which maybe persistently abnormal, especially those that indicate the tendency of the blood to clot slowly.
A shrunken liver (cirrhosis) may also be found. One of the grievous outcomes of this disease is the tendency to develop liver cancer or hepatocellular carcinoma.

When nerves are affected, children have severe pain, often in the legs, associated with rigid legs/ body (hypertonia), vomiting, weakness and  sometimes paralysis.

Kidney involvement can cause rickets ie weakness in bones leading to deformity  in the bones in form of bowing of legs, wide wrists etc. Occasionally,  the kidneys are enlarged and  may be felt on examination of the abdomen.
Rarely a heart problem involving thickening of heart muscles (Hypertrophic cardiomyopathy), is seen.

  • How do we diagnose tyrosinemia?

Hepatorenal tyrosinemia is confirmed by a urinary test- Urine For Succinyl Acetone.- which is a major toxic by-product of disruption in tyrosine breakdown.
Other tests which can be done include serum alpha feto protein (AFP) which when very high suggests tyrosinemia very strongly in appropriate clinical settings; even in absence of carcinoma.
Definitive test to establish diagnosis is to study the enzyme – FAH – activity level in lymphocytes, but is not freely available in India.

  • What are the other tests which may be needed for diagnosis of tyrosinemia?


Other tests which may be ordered by the doctors include :

  • complete blood count  and haemoglobin- for anemia and infections;
  • liver function tests – to assess damage to the liver.
  • Prothrombin time- to assess coagulation problems
  • Plasma amino acids – high level of tyrosine and other amino acids in blood
  • Certain urine tests may be ordered to assess the function of the kidney (urine pH, urine glucose etc).
  • Ultrasonography may also be done to assess the damage to kidney which may show calcium deposits in the kidney (nephrocalcinosis).


  • What is the risk of development of hepatocellular carcinoma?

Hepatorenal tyrosinemia carries a significant long term risk of development of hepatocellular carcinoma. Some studies have reported rates up to 75%.


  • How do we treat tyrosinemia?

Since tyrosinemia is a inherited disease with a problem in body's ability to breakdown certain amino acids, the defect is permanent. The disease can be CONTROLLED though not successfully CURED with the available interventions.

In this disease, since the body cannot utilise tyrosine, diet restriction is an important part of the treatment. Diet low in tyrosine and phelylalanine- another amino acid that can be converted to tyrosine in our body.
The following foods should be avoided as  they contain large amounts of  these amino acids:

  •  meat, eggs, cheese, milk
  •  Regular flour,
  • dried beans,
  • nuts and peanut butter and must also be limited.
  • Soya
  • Bread, cakes, chocolates, biscuits.


The following foods can be consumed safely:

  • Fruits: banana, apple, pear
  • Vegetables: tomatoes, cucumber, mushrooms
  • Sweets
  • Butter, vegetable oil

Young babies require small amounts of tyrosine in the diet. Hence specially designed                                        formulas may need to be given which are low in tyrosine. A drug – nitisinone (NTBC) has been proven to reduce the disease progression and have better long term outcomes. It may reduce the need of liver transplant. It may not prevent the development of hepatocellular carcinoma or cure the disease.
Liver transplant remains the  most effective possible cure for these patients.

  • Is there any way to prevent this disease in siblings of an affected child?

This disease is transmitted in an autosomal recessive pattern- meaning that every pregnancy has a 25% chance that the foetus can be affected.
Prenatal diagnosis (diagnosis in pregnancy) by chorionic villous sampling or assessment of succinylacetone in amniotic fluid can be done.
Newborn screening for tyrosinemia is also coming up in many centres in India. Early detection and intervention have shown promising results on survival of these children abroad, though results from India are lacking.



Important articles on tyrosinemia:

  • Tyrosinemia: a report of three cases from India.

Shah I. Indian J Gastroenterol. 2013 Mar;32(2):123-6. doi: 10.1007/s12664-012-0300-3.

  • Outcome of children with hereditary tyrosinaemia following newborn screening.

McKiernan PJ, Preece MA, Chakrapani A. Arch Dis Child. 2015 Jan 6. pii: archdischild-2014-306886. doi: 10.1136/archdischild-2014-30688.

  • Hepatocellular carcinoma in tyrosinemia type 1 without clear increase of AFP.

van Ginkel WG, Gouw AS, van der Jagt EJ, de Jong KP, Verkade HJ , van Spronsen FJ. Pediatrics. 2015 Mar;135(3):e749-52. doi: 10.1542/peds.2014-1913. Epub 2015 Feb 9.


  • HCC prevalence and histopathological findings in liver explants of patients with hereditarytyrosinemia type 1.

eda Neto J, Leite KM, Porta A, Fonseca EA, Feier FH, Pugliese R, Miura IK, Chapchap P, Porta G. Pediatr Blood Cancer. 2014 Sep;61(9):1584-9. doi: 10.1002/pbc.25094. Epub 2014 May 22.


  • Early effect of NTBC on renal tubular dysfunction in hereditary tyrosinemia type 1.

Maiorana A, Malamisura M, Emma F, Boenzi S, Di Ciommo VM, Dionisi-Vici C. . Mol Genet Metab. 2014 Nov;113(3):188-93. doi: 10.1016/j.ymgme.2014.07.021. Epub 2014 Aug 1.

  • Impaired cognitive functioning in patients with tyrosinemia type I receiving nitisinone.

Bendadi F, de Koning TJ, Visser G, Prinsen HC, de Sain MG, Verhoeven-Duif N, Sinnema G, van Spronsen FJ, van Hasselt PM. J Pediatr. 2014 Feb;164(2):398-401. doi: 10.1016/j.jpeds.2013.10.001. Epub 2013 Nov 14.

  • Behavioral and intellectual functioning in patients with tyrosinemia type I.

Pohorecka M, Biernacka M, Jakubowska-Winecka A, Biernacki M, Kuśmierska K, Kowalik A, Sykut-Cegielska J. Pediatr Endocrinol Diabetes Metab. 2012;18(3):96-100.

  • Identification of NovelMutations in FAH Gene and Prenatal Diagnosis of Tyrosinemia in Indian Family.

Sheth JJ, Ankleshwaria CM, Pawar R, Sheth FJ. Case Rep Genet. 2012;2012:428075. doi: 10.1155/2012/428075.



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