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Hereditary Tyrosinemia pp 111–122Cite as

Neurological and Neuropsychological Problems in Tyrosinemia Type I Patients

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

Abstract

Clinically, Hereditary Tyrosinemia type I (HTI) is especially characterized by severe liver dysfunction in early life. However, recurrent neurological crises are another main finding in these patients when they are treated with a tyrosine and phenylalanine restricted diet only. This is caused by the accumulation of δ-aminolevulinic acid due to the inhibitory effect of succinylacetone on the enzyme that metabolizes δ-aminolevulinic acid. Due to the biochemical and clinical resemblance of these neurological crises and acute intermittent porphyria, this group of symptoms in HTI patients is mostly called porphyria-like-syndrome. The neurological crises in HTI patients disappeared after the introduction of treatment with 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3-cyclohexanedione (NTBC). However, if NTBC treatment is stopped for a while, severe neurological dysfunction will reappear.

If NTBC treatment is started early and given continuously, all clinical problems seem to be solved. However, recent research findings indicate that HTI patients have a non-optimal neurocognitive outcome, showing (among others) a lower IQ and impaired executive functioning and social cognition. Unfortunately the exact neuropsychological profile of these HTI patients is not known yet, neither are the exact pathophysiological mechanisms underlying these impairments. It may be hypothesized that the biochemical changes such as high blood tyrosine or low blood phenylalanine concentrations are important in this respect, but an direct toxic effect of NTBC or production of toxic metabolites (that previously characterized the disease before introduction of NTBC) cannot be excluded either. This chapter discusses the neurological and neuropsychological symptoms associated with HTI in detail. An extended section on possible underlying pathophysiological mechanisms of such symptoms is also included.

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Abbreviations

5-ALA:

δ-aminolevulinic acid

CSU:

Cerebral spinal fluid

HTI:

Hereditary tyrosinemia type I

HTII:

Hereditary tyrosinemia type II

HTIII:

Hereditary tyrosinemia type III

LAT-1:

Late neutral aminoacid-1 transporter

LNAA:

Large neutral amino acid

NTBC:

2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3-cyclohexanedione

PKU:

Phenylketonuria

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Authors and Affiliations

  1. Beatrix Children’s Hospital, Division of Metabolic Diseases, University of Groningen, University Medical Center of Groningen, HPC CA33, Antwoordnummer 333, 9700 VB, Groningen, The Netherlands

    Willem G. van Ginkel, Rianne Jahja & Francjan J. van Spronsen

  2. Department of Clinical Neuropsychology, University of Leiden, Leiden, The Netherlands

    Stephan C. J. Huijbregts

Authors
  1. Willem G. van Ginkel
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  2. Rianne Jahja
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  3. Stephan C. J. Huijbregts
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  4. Francjan J. van Spronsen
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Correspondence to Francjan J. van Spronsen .

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Editors and Affiliations

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

    Robert M. Tanguay

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van Ginkel, W.G., Jahja, R., Huijbregts, S.C.J., van Spronsen, F.J. (2017). Neurological and Neuropsychological Problems in Tyrosinemia Type I Patients. 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_10

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