Glutaric Aciduria Type 1 and Acute Renal Failure: Case Report and Suggested Pathomechanisms

  • Marcel du Moulin
  • Bastian Thies
  • Martin Blohm
  • Jun Oh
  • Markus J. Kemper
  • René Santer
  • Chris Mühlhausen
Research Report
Part of the JIMD Reports book series (JIMD, volume 39)

Abstract

Glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial matrix enzyme glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in tissues and body fluids. During catabolic crises, GA1 patients are prone to the development of striatal necrosis and a subsequent irreversible movement disorder during a time window of vulnerability in early infancy. Thus, GA1 had been considered a pure “cerebral organic aciduria” in the past. Single case reports have indicated the occurrence of acute renal dysfunction in children affected by GA1. In addition, growing evidence arises that GA1 patients may develop chronic renal failure during adulthood independent of the previous occurrence of encephalopathic crises. The underlying mechanisms are yet unknown. Here we report on a 3-year-old GA1 patient who died following the development of acute renal failure most likely due to haemolytic uraemic syndrome associated with a pneumococcal infection. We hypothesise that known GA1 pathomechanisms, namely the endothelial dysfunction mediated by 3OHGA, as well as the transporter mechanisms for the urinary excretion of GA and 3OHGA, are involved in the development of glomerular and tubular dysfunction, respectively, and may contribute to a pre-disposition of GA1 patients to renal disease. We recommend careful differential monitoring of glomerular and tubular renal function in GA1 patients.

Abbreviations

3OHGA

3-Hydroxyglutaric acid

E-IMD

European registry and network for intoxication-type metabolic diseases

GA

Glutaric acid

GA1

Glutaric aciduria type 1

GCDH

Glutaryl-CoA dehydrogenase

GFR

Glomerular filtration rate

HUS

Haemolytic uraemic syndrome

LDH

Lactate dehydrogenase

OAD

Organic aciduria

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Marcel du Moulin
    • 1
  • Bastian Thies
    • 1
  • Martin Blohm
    • 1
  • Jun Oh
    • 1
  • Markus J. Kemper
    • 1
  • René Santer
    • 1
  • Chris Mühlhausen
    • 1
  1. 1.University Children’s Hospital, University Medical Center Hamburg-EppendorfHamburgGermany

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