Diagnosis and the importance of early treatment of tyrosinemia type 1: A case report.

Autor: Škaričić A; Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia., Zekušić M; Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia., Fumić K; Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia., Rogić D; Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia., Uroić V; Department of Nutrition and Dietetics, University Hospital Center Zagreb, Zagreb, Croatia., Petković Ramadža D; Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia.; University of Zagreb, School of Medicine, Zagreb, Croatia., Žigman T; Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia., Barić I; Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia.; University of Zagreb, School of Medicine, Zagreb, Croatia.
Jazyk: angličtina
Zdroj: Clinical mass spectrometry (Del Mar, Calif.) [Clin Mass Spectrom] 2019 Feb 02; Vol. 12, pp. 1-6. Date of Electronic Publication: 2019 Feb 02 (Print Publication: 2019).
DOI: 10.1016/j.clinms.2019.01.005
Abstrakt: 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.
(© 2019 The Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL). Published by Elsevier B.V.)
Databáze: MEDLINE
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