Tyrosinemia type 1 is an autosomal recessive aminoacidopathy caused by
fumarylacetoacetate hydrolase (FAH) deficiency. Consequently,
tyrosine and its metabolites accumulate, resulting in liver and kidney toxicity. Symptoms of the disease usually manifest after three weeks of life and include
vomiting,
failure to thrive,
hepatomegaly,
jaundice,
bleeding diathesis,
rickets and renal tubular dysfunction. Untreated, the disease eventually progresses to liver or
kidney failure and generally results in a fatal outcome. Expedient diagnosis is critical because an early start of treatment can increase the likelihood of a positive outcome. Here, we report on a male newborn with a family history positive for
tyrosinemia type 1 who was subjected to a metabolic work-up immediately after birth.
Amino acids were quantified by tandem mass spectrometry coupled with ultra performance liquid chromatography. Urinary organic
acids were analyzed on capillary gas chromatography coupled with mass spectrometry.
DNA analysis of the FAH gene was performed by Sanger sequencing. On the first day of life, the patient's plasma
amino acids showed an increased
tyrosine concentration, while urine organic
acids detected
succinylacetone, a
tyrosine metabolite specific for
tyrosinemia type 1. The patient's
DNA analysis revealed homozygosity of the c.554-1G > T mutation in the FAH gene, which was consistent with the diagnosis.
Nitisinone treatment, combined with a
dietary restriction of
tyrosine and
phenylalanine, was introduced immediately. Regular visits and measurement of
amino acid concentrations, which enables
therapy adjustment and treatment efficiency monitoring in patients with
tyrosinemia type 1, has continued over the past 4+ years, and is expected to continue.