Cynthia P. Cordero

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

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.

AB107. Challenges in the management of patients with maple syrup urine disease diagnosed by newborn screening in a developing country

Maple syrup urine disease (MSUD) is a rare inborn error of metabolism resulting from a deficiency in the branched-chain alpha-ketoacid dehydrogenase complex. MSUD has been reported to be the most common inborn error of metabolism in the Philippines. This study describes all patients with MSUD patients diagnosed through newborn screening during its first two years of implementation and the challenges encountered during their medical management. We reviewed the medical records of all patients diagnosed with MSUD by newborn screening in the Philippines from its initiation in July 2012 to June 2014. There were 24 patients diagnosed with MSUD by newborn screening for the two-year period. The mean age at newborn screening is 4 days. All patients needed hospital admission. The most common complication during hospital admission was infection, needing intravenous antibiotics which were given to 21 of the patients. Out of the 24 diagnosed, 16 (66.67%) of patients are alive, while 8 (33.33%) have died. Several neurologic and non-neurologic complications have been observed during the follow-up of the patients. The common challenges of MSUD diagnosis and management in a low-resource setting identified in this study were late diagnosis, lack of access to metabolic specialists and medical supplies, nosocomial septicaemia, and protein deficiency. Aside from early properly-timed collection, improvement in other logistical concerns such as an efficient system of sending and delivery of samples will also help in earlier diagnosis. Mechanisms of transfer of critically ill patients, albeit challenging in our setting due to geographical concerns, must be improved. Hospitals in difficult-to-reach areas must be equipped to handle critical metabolic cases when transfers are not possible. Newborn screening has been proven to improve outcome in patients diagnosed to have MSUD but the success of the newborn screening program in preventing disability is also dependent on improvements in other aspects of healthcare.

Factors affecting mortality among leptospiral acute renal failure cases at the Philippine General Hospital

Objective: To determine factors associated with mortality among leptospiral acute renal failure (ARF) cases. Mortality rate in the Philippines for this group of patients is high (ll-69%). Design: A prospective study. Setting: Philippine General Hospital Adult Major Medical Unit, PGHAMMU. A tertiary hospital. Participants: 149 patients admitted at the PGH-AMMU from January 1, 1992 to December 31, 1993 with presumptive evidence of leptospirosis by the WHO criteria and with one of the following: positive leptospirosis micro agglutination titer or positive leptospiral culture of urine/blood/csf or in cases of early death, majority vote of 4 clinicians. Potential Factors/Predictors: Age, sex, treatment (pharmacologic combination), no. of days exposure to flood waters, vol. of fluids infused, oliguria time, admission levels of hemoglobin, wbc, platelet, bun, creatinine, potassium, sgot, sgpt and direct &a indirect bilirubin, oliguria aaf, need for dialysis, cardiopulmonary complications. Main Outcome Measure: Mortality at hospital discharge. Results: Age, potassium level, the treatment received, cardiopulmonary complications & oliguria were found to be the important factors by bivaria-2 analysis. Stepwise logistic regression yielded age, potassium, pulmonary hemorrhage, OR = 24.3 (95% CI: 6.8-86.9), carditis, OR = 3.66 (95% CI 1.3-10.6) as the important predictors. Conclusions: Cardiopulmonary complications were the more important predictors identified. Age &potassium were also found important. Oliguria &a treatment, although found important by bivariate analysis were not found important by logistic regression. This could be due to the fact that these factors are more distal predictors of mortality & their effects cannot be detected once complications occur. Thus management of leptospirosis can be directed towards prevention of complications.