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Initial presentation, management and follow-up data of 33 treated patients with hereditary tyrosinemia type 1 in the absence of newborn screening

Authors :
Hela Hajji
Apolline Imbard
Anne Spraul
Ludmia Taibi
Valérie Barbier
Dalila Habes
Anaïs Brassier
Jean-Baptiste Arnoux
Juliette Bouchereau
Samia Pichard
Samira Sissaoui
Florence Lacaille
Muriel Girard
Dominique Debray
Pascale de Lonlay
Manuel Schiff
Source :
Molecular Genetics and Metabolism Reports, Vol 33, Iss , Pp 100933- (2022)
Publication Year :
2022
Publisher :
Elsevier, 2022.

Abstract

Hereditary tyrosinemia type 1 (HT1) is a rare autosomal recessive disorder of phenylalanine and tyrosine catabolism due to a deficiency of fumarylacetoacetate hydrolase. HT1 has a large clinical spectrum with acute forms presenting before six months of age, subacute forms with initial symptoms occurring between age 6 and 12 months, and chronic forms after 12 months of age. Without treatment, HT1 results in the accumulation of toxic metabolites leading to liver disease, proximal tubular dysfunction, and porphyria-like neurological crises. Since the early nineties, the outcome of HT1 has dramatically changed due to its treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC, nitisinone). In some countries, HT1 is included in the newborn screening program based on the analysis of succinylacetone concentration on dried blood spots.In the present study, we report clinical and laboratory parameters data on 33 HT1 patients focusing on clinical presentation and therapeutic management at the time of diagnosis. Eighteen patients were diagnosed with the acute form (median age at presentation 2.5 months), 6 with the subacute form (median age at presentation 10 months), and 5 with the chronic form of HT1 (median age at presentation 15 months). Four patients were diagnosed pre-symptomatically in the setting of a family history of HT1. Among the 29 symptomatic patients, hepatomegaly was found in 83% of patients and prolonged coagulation times due to hepatocellular insufficiency was observed in 93% of patients. HT1 diagnosis was confirmed by increased urine succinylacetone in all patients. All patients but 2 were treated with nitisinone immediately at diagnosis. During follow-up, 2 patients received liver transplant for high grade dysplasia or hepatocellular carcinoma, 10 patients exhibited some form of neurocognitive impairments.Our data confirm that HT1 is a severe treatable liver disease that should be detected at the earliest, ideally by newborn screening and appropriately treated.

Details

Language :
English
ISSN :
22144269
Volume :
33
Issue :
100933-
Database :
Directory of Open Access Journals
Journal :
Molecular Genetics and Metabolism Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.06ee16d9c5f84e49b379a7616bb8c55f
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ymgmr.2022.100933