Mary Anne D. Chiong1, Cynthia P. Cordero2, Esphie Grace D. Fodra1, Judy S. Manliguis1, Cristine P. Lopez1, Leslie Michelle M. Dalmacio3
Background and objective: Maple syrup urine disease (MSUD) is the most common inborn error of metabolism in the country. The main cause of the neuropathology is still not well established although the accumulation of branched chain amino acids (BCAA) and alteration in large neutral amino acids (LNAA) as well as energy deprivation have been suggested. It is the aim of the study to determine the plasma amino acid and urine organic acid profiles of Filipino patients with MSUD and correlate the findings with their neurologic features.
Methods: Twenty six Filipino patients confirmed to have 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. Their neurologic features were reviewed and correlated with the results of their plasma amino acid and urine organic acid profiles.
Results: Majority of the patients with MSUD had developmental delay/intellectual disability (88%), speech delay (69%) and seizures (65%). The amino acid profile of MSUD patients 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 other Krebs cycle metabolites that would indicate possible energy perturbation were not found in significant amounts. There were also no metabolite markers in the plasma amino acids or urine organic acids that correlated significantly with the neurologic features. The most remarkable finding in this study was the discriminant analysis done on 7 clinically and statistically significant important amino acids in the plasma wherein elevations in leucine, isoleucine, alloisoleucine, phenylalanine and threonine, and decreased levels of glutamine and alanine clearly defined the boundary between an MSUD case and control.
Conclusions: The findings suggest that there could be altered LNAA metabolism among patients with MSUD when the BCAAs are elevated in plasma. A set of plasma amino profile comprising of 7 amino acids may be suggestive of MSUD if altogether present. The urine organic acid analysis showed elevated excretions of the branched chain ketoacids and succinate. However, the above biochemical findings were not significantly correlated with the neurologic features of patients with MSUD, thus, there could be other unknown factors that cause the neurologic impairments in MSUD other than the elevated BCAAs and their corresponding ketoacids or the elevated LNAAs.
