A case report of two siblings with hypertyrosinemia type 1 presenting with hepatic disease with different onset time and severity.
Mol Genet Metab Rep
; 32: 100892, 2022 Sep.
Article
en En
| MEDLINE
| ID: mdl-35800472
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by a defect in fumarylacetoacetate hydroxylase (FAH) encoded by the FAH gene. Patients with HT1 disorder present with increased blood tyrosine, succinyl acetoacetate, and succinyl acetone levels, and develop clinical manifestations including liver failure, kidney tubular dysfunction, growth failure, rickets, pseudo-porphyric crises, and hepatocellular carcinoma. We encountered two siblings with HT1. Among the siblings, the elder brother developed acute liver failure with coagulopathy at the age of 2 months and was rescued by liver transplantation (LT) following combination therapy with continuous hemodiafiltration and plasma exchange. The younger sister was followed up from the prenatal period for signs of HT1 due to prior history of the condition in her sibling. She was initially considered a carrier of HT1 owing to the lack of overt signs of the disease and negative urine screening for succinyl acetone (SA). She was eventually diagnosed with HT1 because of liver disorder at 9 months of age, associated with a positive urine SA result. Her disease state was controlled by treatment with nitisinone (NTBC). DNA analysis of both siblings identified heterozygous status for a previously reported FAH pathogenic allele (c.782C > T) and a novel likely pathogenic variant (c.688C.G). The siblings have stable lives with no developmental delay or impaired growth. NTBC treatment is effective in preventing the progression of liver and kidney diseases. However, even in cases treated without LT, clinicians should follow up the clinical outcomes over long term, as patients may require LT when developing complications, such as hepatocellular carcinoma.
ALF, acute liver failure; CHDF, continuous hemodiafiltration; FAH; FAH, fumarylacetoacetate hydroxylase; FFP, fresh frozen plasma; HCC, hepatocellular carcinoma; HT1, hereditary tyrosinemia type 1; Hereditary tyrosinemia type 1; LT, liver transplantation; Liver transplantation; NBS, newborn mass screening; NTBC, nitisinone; Nitisinone; PE, plasma exchange; PT, prothrombin time; SA, succinyl acetone; SD, standard deviation
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
/
Screening_studies
Idioma:
En
Revista:
Mol Genet Metab Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos