Is Expanded Newborn Screening Adequate to Detect Indian Biochemical Low Excretor Phenotype Patients of Glutaric Aciduria Type I?
To investigate if expanded newborn screening using tandem mass spectroscopy (TMS) is adequate to detect low excretor phenotype in Indian Glutaric aciduria type I (GA-I) patients.
Ten GA-I patients were investigated for blood glutaryl carnitine (C5DC) levels on dried blood spot (DBS) by tandem mass spectroscopy and urine glutaric acid (GA) and 3-hydroxyglutaric acid (3-OH-GA) by gas chromatography-mass spectroscopy. The student’s T test and Pearson’s correlation were applied to draw a relationship between various biochemical parameters. Further confirmation of low excretors by DNA mutation analysis in the glutaryl CoA dehydrogenase (GCDH) gene was performed by polymerase chain reaction and Sangers sequencing.
Among 10 GA-I patients, 7 patients were found to have high excretor, and 3 were found to have low excretor phenotype. The low excretors were found to have GCDH gene mutations. The mean C5DC levels in high and low excretors were 2.61 ± 2.02 μmol/L and 2.31 ± 1.00 μmol/L, respectively. In high excretors, C5DC levels correlated with GA (r = 0.95). In low excretors, C5DC levels correlated with 3-OH-GA (r = 0.99). No significant difference was found between C5DC levels of high and low excretors (p = 0.82).
The MS/MS, C5DC screening is a sensitive technique and detected 10 GA-I patients. Irrespective of the urine organic acid levels, Indian GA-I patients including low excretors seem to have a significantly elevated C5DC level and well above the stipulated cut-off values and therefore, expanded newborn screening is probably adequate to diagnose them.
KeywordsGlutaric aciduria type I Glutaryl carnitine Newborn screening Tandem mass spectroscopy Glutaric acid
All the authors have revised the manuscript and contributed to the drafting of the article. They confirm that the manuscript is an original version and has not been published in any other scientific journal or elsewhere; MS has performed the biochemical analysis and genetic analysis and drafted the manuscript. MK has been the referral physician for neonatal resuscitation and metabolic and nutritional management of the patient and has validated the results. KVTP and VAB have helped in cross checking the genetic reports and framing the script. All authors read and approved the final manuscript. Prof. Shyam Kumar Vootla, Professor and Chairman, Department of Biotechnology and Microbiology, Karnatak University, Dharwad, is the guarantor for this article.
Compliance with Ethical Standards
Conflict of Interest
Source of Funding
Maulana Azad National Fellowship F1–17.1/2017–18/MANF-2017-18-KAR-75132.
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