Plasma amino acid and urine organic acid profiles of Filipino patients with maple syrup urine disease (MSUD) and correlation with their neurologic features

Mary Anne D Chiong; Marilyn A Tan; Cynthia P Cordero; Esphie Grace D Fodra; Judy S Manliguis; Cristine P Lopez; Leslie Michelle M Dalmacio

doi:10.1016/j.ymgmr.2016.10.004

Plasma amino acid and urine organic acid profiles of Filipino patients with maple syrup urine disease (MSUD) and correlation with their neurologic features

Mol Genet Metab Rep. 2016 Oct 12:9:46-53. doi: 10.1016/j.ymgmr.2016.10.004. eCollection 2016 Dec.

Authors

Mary Anne D Chiong¹, Marilyn A Tan², Cynthia P Cordero³, Esphie Grace D Fodra¹, Judy S Manliguis¹, Cristine P Lopez¹, Leslie Michelle M Dalmacio⁴

Affiliations

¹ Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines.
² Department of Pediatrics, Section of Neurology, Philippine General Hospital, University of the Philippines Manila, Philippines.
³ Department of Clinical Epidemiology, University of the Philippines Manila, Philippines.
⁴ Department of Biochemistry, University of the Philippines Manila, Philippines.

Abstract

Background: Maple syrup urine disease (MSUD) is the most common inborn error of metabolism in the country. The cause of the neuropathology is still not well established although accumulation of branched chain amino acids (BCAA) and alteration in large neutral amino acids (LNAA) as well as energy deprivation are suggested. It is therefore the aim of this study to determine the plasma amino acid and urine organic acid profiles of patients with MSUD and correlate the findings with their neurologic features.

Methodology: Twenty six Filipino patients with MSUD were studied in terms of their plasma amino acid and urine organic acid profiles. Their results were compared with 26 age and sex matched controls. The neurologic features were correlated with the results of the plasma amino acids and urine organic acids.

Results: Majority of the patients with MSUD had developmental delay/intellectual disability (88%), speech delay (69%), and seizures (65%). Their amino acid profiles revealed low glutamine and alanine with high levels of leucine, isoleucine, phenylalanine, threonine and alloisoleucine compared to controls (p < 0.05). The urine organic acids showed significantly elevated excretion of the branched chain ketoacids and succinate (p < 0.05). However there were no biochemical markers that correlated significantly with the neurologic features.

Conclusion: The findings suggest that there could still be altered LNAA metabolism among patients with MSUD when the BCAAs are elevated. Although the biochemical findings were not significantly correlated with the neurologic features, the study showed that prevention and avoidance of neurologic disturbances may still rely primarily on early diagnosis and prompt institution of treatment, along with strict compliance with the dietary regimen and maintenance of good metabolic control over time.

Keywords: BCAA, branched chain amino acids; BCKAD, branched chain keto acid dehydrogenase; LNAA, large neutral amino acids; MSUD; MSUD, maple syrup urine disease; Neurologic features; Plasma amino acids; Urine organic acids.