Tyrosinaemia is a rare genetic disease caused by the dysfunction of the enzyme that is involved in breaking down the tyrosine, an amino acid found in food proteins. The disease is inherited in an autosomal recessive pattern, that means that the gene responsible for the disease is recessive. Therefore, a child will be affected if it inherits two defective (recessive) genes, one from each parent. When the parents are not affected, they are called “carriers” of this recessive gene. The dysfunction of this enzyme results in an accumulation of toxic metabolic products that damage the liver and the kidneys and an accumulation of tyrosine that affects the development of the nervous system, of the skin and the eyes. About 1 in 100,000 individuals are affected worldwide. The disease is particularly common in a region in Quebec. In northern Europe, the incidence varies between 1 in 12,000 and 1 in 100,000 individuals. At present, tyrosinaemia is not part of newborn screening in Switzerland.

The main symptoms of tyrosinaemia appear between birth and the third month of life and include: jaundice (icterus), abdominal distension, nasal bleeding, poor gain in weight, vomiting and diarrhoea. Mental retardation, skin lesions and ophthalmological problems may occur later. A blood analysis and a urinalysis must be carried out for the diagnosis in order to identify the specific toxic metabolites of the disease.

Children at risk can be diagnosed before birth thanks to an analysis of amniotic fluid. Since the identification of the responsible gene, a blood sample taken from the parents also makes it possible to detect the carriers and to determine the risk of having a child affected by tyrosinaemia.

If left untreated, the disease is fatal in most cases. When the disease is diagnosed early, the child can be treated with nitinisone or NTBC that aims at limiting the production of toxic substances by the liver. A protein-free diet is added in many cases. In order to avoid nutritional deficiencies, the children receive protein supplements specially produced without tyrosine. When the treatment and the diet are not enough or when the diagnosis is made late, the only treatment option is a liver transplant. The liver transplant has contributed, together with NTBC, to improve the future of these patients. Besides the neurological, hepatic and renal risks, tyrosinaemia is dreaded since it is associated with hepatocellular carcinoma (liver cancer). When a suspicious node of the liver and an increase in the tumour marker (alpha-fetoprotein) are present, the transplant is indicated.

Dr. Alexandra Tsouka