Tyrosinemia I

Introduction
Autosomal recessive Inheritance, deficiency of fumarylacetoacetase, Major sequelae of
liver failure and hepatocellular carcinoma

Clinical Features
Neonatal
Liver failure (usually well preserved transaminases however)
jaundice
ascites
edema
Renal tubular dysfunction
vomiting
diarrhea
hypoglycemia
sepsis and particularly bleeding
Infancy/childhood
Above plus
Rickets
failure to thrive
hepatosplenomegaly
neurological deficit
hypotonia
asymptomatic until developing hepatocellular carcinoma
Consequence
Cirrhosis, hepatocellular carcinoma

Diagnosis
Newborn screen
Tandem mass spectrometry for *
Confirmation
Elevated urinary succinylacetone; also look for elevated urinary
4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate and d-ALA liver biopsy for assay of
fumarylacetoacetase activity (though enzyme mosaicism may obscure the result).

Treatment
- Dietary restriction of tyrosine and phenylalanine. Aim to keep tyrosine level below
   500µmol/l
- Treatment with NTBC (2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione) to
   block metabolism (see figure) prior to production of hepatotoxic fumarylacetoacetate
   plus dietary restriction of phenylalanine and tyrosine.
- Liver transplantation when indicated has good results. Renal transplant secondary to
   nephrocalcinosis may also be required.
- 1,25-hydroxyvitamin D may be required to heal rickets.

Situations that risk metabolic decompensation
*

Monitoring
Clinical well being of the child.
Ultrasound/CT of the liver.
Alpha fetoprotein
Liver function tests, clotting studies, calcium, potassium and phosphate
Tyrosine levels

STAT emergency treatment
Supportive treatment is essential. Limit tyrosine and phenylalnine to a minimum. Closely
monitor clotting factors, albumin, calcium, phosphate, electrolytes and acid/base status.
Correct as indicated

Infection/Immunization
Any infection can potentially lead to metabolic decompensation. Therefore its prevention
and/or early intervention is of particular importance. For this and other reasons
immunizations must be kept on track. This includes a yearly vaccine for influenza for
all children with Tyrosinemia type I. There is no contraindication to immunization
because of Tyrosinemia type I, but patients and physicians should be alerted to the
need for immediate evaluation if high fever, lethargy or vomiting occurs in the first 24h.
After an immunization without any other clinical symptoms, administration of
acetaminophen or ibuprofen is warranted.

Surgical/surgical procedures
*
Growth and development
As these patients may have failure to thrive AND are maintained on a restricted diet it is crucial
to closely monitor all growth parameters on a regular basis. In cases with neurological deficits
the child should be integrated into an early intervention program and developmental progress
closely monitored by both the metabolic team and the primary care provider.

Figure