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

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.

Appendices

Synopsis

We report on a 3-year-old GA1 patient with acute renal failure most likely due to haemolytic uraemic syndrome associated with a pneumococcal infection. Endothelial dysfunction and renal proximal tubule accumulation of GA1 metabolites may contribute to acute and chronic glomerular and tubular dysfunction in GA1 patients.

Compliance with Ethics Guidelines

Conflict of Interest Statement

Marcel du Moulin, Bastian Thies, Martin Blohm, Jun Oh, Markus J. Kemper, René Santer and Chris Mühlhausen declare that they have no conflict of interest.

Informed Consent

The study does not contain any identifying information about patients.

This chapter does not contain any studies with human or animal subjects performed by any of the authors.

Details of the Contributions of Individual Authors

Marcel du Moulin: Dr. du Moulin cared for the patient, performed collection and analyses of the data, drafted and critically reviewed the manuscript and approved the final manuscript as submitted.

Bastian Thies: Dr. Thies cared for the patient, performed collection and analyses of the data, drafted and critically reviewed the manuscript and approved the final manuscript as submitted.

Martin Blohm: Dr. Blohm cared for the patient, especially with regard to the intensive care management, carried out critical discussions regarding the pathophysiology of the patient, collected and analysed the data, reviewed and revised the manuscript and approved the final manuscript as submitted.

Jun Oh: Dr. Oh carried out and critically discussed the nephrologic treatment of the patient (dialysis procedures), collected and critically discussed the data, reviewed and revised the manuscript and approved the final manuscript as submitted.

Markus J. Kemper: Dr. Kemper carried out and critically discussed the nephrologic treatment of the patient (dialysis procedures), collected and critically discussed the data, reviewed and revised the manuscript and approved the final manuscript as submitted.

René Santer: Dr. Santer carried out and critically discussed the metabolic treatment of the patient, critically analysed and reviewed the collected data, drafted, critically reviewed and revised the manuscript and approved the final manuscript as submitted.

Chris Mühlhausen: Dr. Mühlhausen carried out, critically discussed and reviewed the metabolic treatment of the patient, designed the data collection instruments, coordinated and supervised data collection and analyses, drafted and critically reviewed the manuscript and approved the final manuscript as submitted.