Neonatal screening for glutaryl‐CoA dehydrogenase deficiency

• Published in: Journal of inherited metabolic disease Vol. 27; no. 6; pp. 851 - 859
• Main Authors: Lindner, M., KÖlker, S., Schulze, A., Christensen, E., Greenberg, C. R., Hoffmann, G. F.
• Format: Journal Article
• Language: English
• Published: Dordrecht Kluwer Academic Publishers 01.11.2004; Blackwell Publishing Ltd
• Subjects: Amino Acid Metabolism, Inborn Errors - diagnosis; Amino Acid Metabolism, Inborn Errors - epidemiology; DNA - genetics; Glutaryl-CoA Dehydrogenase; Humans; Infant, Newborn; Neonatal Screening; Oxidoreductases Acting on CH-CH Group Donors - deficiency; Phenotype
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1023/B:BOLI.0000045769.96657.af

Acute encephalopathic crisis in glutaryl‐CoA dehydrogenase deficiency results in an unfavourable disease course and poor outcome, dominated by dystonia, feeding problems, seizures and secondary complications, and quite often leading to early death. The prerequisite for the prevention of irreversible brain damage in this disease is the detection of affected patients and initiation of treatment before the manifestation of such crisis. Apart from macrocephaly there are no signs or symptoms characteristic for this disease in presymptomatic children and, thus, they are usually missed. In some countries, implementation of extended neonatal screening programmes using electrospray ionization tandem mass spectrometry (ESI‐MS/MS) allows detection of affected newborns and start of therapy before onset of neurological complications. This article summarizes recent strategies, pitfalls and shortcomings of a mass screening for glutaryl‐CoA dehydrogenase deficiency using ESI‐MS/MS. Furthermore, an alternative strategy, namely DNA‐based neonatal screening for the Oji‐Cree variant of this disease, is demonstrated. An optimization of diagnostic as well as therapeutic procedures must be achieved before GCDH deficiency unequivocally fullfils the criteria of a reliable and successful newborn screening programme.