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Hereditary Tyrosinemia pp 9–21Cite as

Biochemical and Clinical Aspects of Hereditary Tyrosinemia Type 1

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 959))

Abstract

Inborn errors of metabolism (IEMs) are a group of diseases involving a genetic defect that alters a metabolic pathway and that presents usually during infancy. The tyrosine degradation pathway contains five enzymes, four of which being associated with IEMs. The most severe metabolic disorder associated with this catabolic pathway is hereditary tyrosinemia type 1 (HT1; OMIM 276700). HT1 is an autosomal recessive disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH), the last enzyme of the tyrosine catabolic pathway. Although a rare disease worldwide, HT1 shows higher incidence in certain populations due to founder effects. The acute form of the disease is characterized by an early onset and severe liver failure while the chronic form appears later and also involves renal dysfunctions. Until 1992 the only treatment for this disease was liver transplantation. Since then, NTBC/Nitisone (a drug blocking the pathway upstream of FAH) is successfully used in combination with a diet low in tyrosine and phenylalanine, but patients are still at risk of developing hepatocellular carcinoma. This chapter summarizes the biochemical and clinical features of HT1.

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Abbreviations

ALA:

δ-aminolevulinic acid

ALAD:

δ-aminolevulinic acid dehydratase

BER:

Base excision repair

FAA:

Fumaryl acetoacetate

FAH:

Fumarylacetoacetate hydrolase

GSH:

Glutathione

HCC:

Hepatocellular carcinoma

HGA:

Homogentisic acid

HGO:

Homogentisic acid oxidase

HPD:

p-hydroxyphenylpyruvate dioxygenase

HT1:

Hereditary tyrosinemia

IEM:

Inborn errors of metabolism

MAA:

Maleyl acetoacetate

MAAI:

Maleyl acetoacetate isomerase also known as (ζ) 1 GSTZ1

OLT:

Orthotopic liver transplantation

PAH:

Phenylalanine hydroxylase

SAA:

Succinylacetone

TAT:

Tyrosine aminotransferase

TCA:

Trichloroacetic acid cycle

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Acknowledgements

The work on HT1 in the RMT’s lab was supported by grants from the Canadian Institutes of Health Research (CIHR) and Fondation du Grand Défi Pierre Lavoie.

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  1. Laboratoire de génétique cellulaire et développementale, Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de médecine, Institut de biologie intégrative et des systèmes (IBIS) and PROTEO, Université Laval, 1030 avenue de la médecine, Québec, QC, G1V 0A6, Canada

    Geneviève Morrow & Robert M. Tanguay

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  1. Geneviève Morrow
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Correspondence to Robert M. Tanguay .

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  1. Department of Molecular Biology, Medical Biochemistry and Pathology, Medical School, Université Laval, Québec, Québec, Canada

    Robert M. Tanguay

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Morrow, G., Tanguay, R.M. (2017). Biochemical and Clinical Aspects of Hereditary Tyrosinemia Type 1. In: Tanguay, R. (eds) Hereditary Tyrosinemia. Advances in Experimental Medicine and Biology, vol 959. Springer, Cham. https://doi.org/10.1007/978-3-319-55780-9_2

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