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Fumaric aciduria: an overview and the first Brazilian case report

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Fumaric aciduria is a rare metabolic disease, with 40 cases reported so far. Fumarase deficiency leads mainly to brain abnormalities, developmental delay, and great accumulation of fumaric acid in urine. This work presents the first case of fumaric aciduria described in Brazil, which presented with some interesting clinical and biochemical findings such as colpocephaly, hepatic alterations, and marked metabolic acidosis since birth. Common findings were ventriculomegaly, hypotonia, and microcephaly. Biochemically, besides the high urinary fumaric acid excretion, atypical elevation of plasma citrulline, tyrosine and methionine levels were also observed. In order to show all features and variants of fumaric aciduria, literature data of 40 patients was reviewed and compared with the case reported here. Findings in all these patients demonstrate that this disorder does not yet have its phenotype completely defined; it is important that more patients be described.

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Abbreviations

AICAR:

5-aminoimidazole-4-carboxamide ribotide

AMP:

adenosine monophosphate

AS:

argininosuccinase

ASL:

adenylosuccinate lyase

ASS:

argininosuccinic synthetase

AST:

aspartate aminotransferase

CPSI:

carbamoylphosphate synthetase I.

FAH:

fumarylacetoacetate hydrolase

FAICAR:

5-formaminoimidazole-4-carboxamide ribotide

FH:

fumarate hydratase

GD:

glutamate dehydrogenase

4-HPPD:

4-hydroxy-phenylpyruvate dioxygenase

IMP:

inosine monophosphate

MAI:

maleylacetoacetate isomerase

ME:

malic enzyme

MDH:

malate dehydrogenase

OT:

ornithine transcarbamoylase

PC:

pyruvate carboxylase

PDHC:

pyruvate dehydrogenase complex

SAICAR:

5-aminoimidazole-(N-succinylcarboxiamide) ribotide

SDH:

succinate dehydrogenase

TAT:

tyrosine aminotransferase

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Acknowledgments

We thank Francisco Radler de Aquino Neto, Luis Nelson L F Gomes, DLE (Diagnósticos Laboratoriais Especializados), Markéta Tesařová and Jean-Pierre Bayley for their contribution to the study.

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Authors and Affiliations

  1. Laboratório de Erros Inatos do Metabolismo (LABEIM), Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Cidade Universitária, Ilha do Fundão, Centro de Tecnologia, bloco A, 536 C, 21941 900, Rio de Janeiro, Brasil

    Gabriella Allegri, Marcia J. Fernandes, Fernanda B. Scalco, Ruth E. Simoni & Maria L. Costa de Oliveira

  2. Centro de Genética Médica, Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brasil

    Patricia Correia & Juan C. Llerena Jr

Authors
  1. Gabriella Allegri
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  2. Marcia J. Fernandes
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  3. Fernanda B. Scalco
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  4. Patricia Correia
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  5. Ruth E. Simoni
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  6. Juan C. Llerena Jr
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  7. Maria L. Costa de Oliveira
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Corresponding author

Correspondence to Gabriella Allegri.

Additional information

Communicated by: Jan Smeitink

Competing interest: None declared.

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Allegri, G., Fernandes, M.J., Scalco, F.B. et al. Fumaric aciduria: an overview and the first Brazilian case report. J Inherit Metab Dis 33, 411–419 (2010). https://doi.org/10.1007/s10545-010-9134-2

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  • DOI: https://doi.org/10.1007/s10545-010-9134-2

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