Tyrosinemia

(Tyrosinosis, hepatorenal tyrosinemia )

Pathology of the metabolism of tyrosine (synthesized from food or tissue protein and phenylalanine). 

Different forms depending on the missing enzyme:

-        hepatic impairment: hepatomegaly, acute liver failure ('liver crises') with coagulopathy or chronic with  micro- and macronodular cirrhosis and significant risk of hepatocellular carcinoma

-        renal impairment: tubular dysfunction with Fanconi syndrome (glycosuria, aminoaciduria); nephromegaly with calcifications; glomerulosclerosis; rickets

-        neurological signs: similar to those of a crisis of porphyria: painful crises, opistothonos, paralysis... because one of the metabolites (succinylacetone) that accumulates inhibits acid  δ-aminolevullinic dehydration.

-        sometimes a symmetric or asymmetric hypertrophic cardiomyopathy (which may improve after the introduction of the medical treatment) or hyperplasia of the islets of Langerhans (hypoglycemia).

Treatment: the daily administration of NTBC (2-2-nitro-4-trifluoromethylbenzoyl-1,3cyclohexanedione) inhibits 4-hydroxy-phenylpyruvate diogenase and rapidly decreases the production of toxic metabolites; dose: 1 mg/kg/day in 2 doses and monitor plasma levels of tyrosine, because if it is > 500 µmol/L there is a risk of ocular toxicity (keratitis, photophobia, opacities, or corneal ulcers); in case of failure of the medical treatment, liver transplantation is performed before the age of 2 years (because of the risk of cancer).


Anesthetic implications: 


References : 

-         Russo PA, Mitchell GA, Tanguay RM. 
Tyrosinemia: a review
Pediatr Developmental Pathol 2001; 4: 212-21.

-         Madan N, Arnon R, Arnon R. 
Evaluation of cardiac manifestations in pediatric liver transplantation candidates. 
Pediatr Transplantation 2012; 16: 318-28.


Updated: September 2018