Assessment of Lymphocyte Subsets in Patients with Maple Syrup Urine Disease

Abstract

SUMMARY T he aim of this work was to assess lymphocyte subsets in patients with maple syrup urine disease in relation to clinical presentation, disease duration, and level of control, aiming at identifying the impact of accumulated toxic metabolites in MSUD on the adaptive immune system. This study included thirty infants and children with maple syrup urine disease, who were attending Genetics Clinic at Children' Hospital, Ain- Shams University. In addition, thirty age and sex-matched children were investigated as a control group. All included patients were subjected to detailed full history with special emphasis on the number of severe infections per year ago of onset of repeated infections, site (s) of infection, duration and response to antimicrobials, family history of similar condition and / or previous sib death. Thorough clinical examination including the general health of the patients, skin, lymph node, chest, heart, and abdominal examination. Laboratory investigations included complete blood count and differential by Coulter Counter. Assessment of leucine, isoleucine, valine levels & the ratio between leucine/alanine & the ratio between leucine/phenylalanine was done to all MSUD patients by MS/MS at time of immune system assessment. 74 Also the mean levels of those parameters in past 3 and 6 months was calculated and used for statistics. Assessment of lymphocyte subsets CD3, CD3+ CD4+, CD3+ CD8+, CD45RA, CD45RO, CD56 and CD19 by flow cytometry. 56.7% (17 patients) of the studied patients were males and 43.3% (13 patients) were females. The mean age of the studied patients was (2.67 years), the mean weight was (13.23 kg) and the mean height was (83.24 cm). 83.3% (25 patients) had positive consanguineous parents, 23.3% (7 patients) had family history of sib death, 16.6% (5 patients) had family history of sib diagnosed MSUD. In the current study, MSUD patients showed a significant increased frequency of infection as compared to controls. In the current study, we found a significant decrease in absolute count of CD3 (P = 0.003), CD3+CD4+ (P = 0.021), CD3+CD8+ (P = 0.008) and CD45RO (P = 0.003) compared to control group. In this study, the mean level of leucine alanine ratio and leucine phenyl alanine ratio in last 6 months had a significant negative correlation with absolute count of CD3+CD4+ (P = 0.037 and P = 0.006, respectively) and CD45RA (P = 0.022 and P = 0.004, respectively). Also the mean level of leucine phenyl