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Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles.
Clément Pontoizeau1,2, Florence Habarou3,4,5, Anaïs Brassier3
1Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, University of Paris Descartes, Institut Imagine, Paris, France. clement.pontoizeau@aphp.fr.
JIMD Reports
|September 28, 2015
Summary
Mitochondrial Acyl-CoA Dehydrogenase (MAD) deficiency is a severe condition. Hyperprolinemia may indicate treatable MAD deficiency, aiding early diagnosis and management.
Area of Science:
- Biochemistry
- Metabolic Disorders
- Neonatal Medicine
Background:
- Classical neonatal-onset glutaric aciduria type 2 (MAD deficiency) is a severe mitochondrial fatty acid oxidation disorder with high mortality.
- Secondary acyl-CoA dehydrogenase dysfunction can arise from riboflavin transporter deficiencies, leading to treatable severe conditions.
Purpose of the Study:
- To investigate the clinical features and diagnostic markers of newborns with biochemical evidence of MAD deficiency.
- To evaluate the role of hyperprolinemia and the proline/alanine ratio in identifying treatable forms of MAD deficiency.
Main Methods:
- Retrospective analysis of nine newborns with biochemical features of MAD deficiency over 10 years.
- Review of patient data including biochemical profiles (amino acids, organic acids, acylcarnitines), genetic testing, and clinical outcomes.
- Analysis of a large cohort (>50,000 samples) to identify potential diagnostic markers.
Main Results:
- Four out of nine identified newborns survived the neonatal period.
- Two premature infants on parenteral nutrition showed iatrogenic riboflavin deficiency; one recovered with supplementation.
- Six of seven tested newborns exhibited hyperprolinemia; the proline/alanine ratio emerged as a potential marker for MAD deficiency.
Conclusions:
- MAD deficiency presents with severe neonatal complications, but some forms are treatable with riboflavin.
- Hyperprolinemia and the proline/alanine ratio may serve as valuable indicators for diagnosing treatable MAD deficiency, improving patient management.
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