Lymphocyte respiration in children with Trisomy 21.

BACKGROUND: This study measured lymphocyte mitochondrial O(2) consumption (cellular respiration) in children with trisomy 21. METHODS: Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O(2)] was determined as a function of time from the phosphorescence decay rates (1/τ) of Pd (II)-meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O(2)] declined linearly with time, confirming the zero-order kinetics of O(2) conversion to H(2)O by cytochrome oxidase. The rate of respiration (k, in µM O(2) min(-1)), thus, was the negative of the slope of [O(2)] vs. time. Cyanide inhibited O(2) consumption, confirming that oxidation occurred in the mitochondrial respiratory chain. RESULTS: For control children (age = 8.8 ± 5.6 years, n = 26), the mean (± SD) value of kc (in µM O(2) per min per 10(7) cells) was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61). For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26), the values of k(c) were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80), p<0.001. Similar results (p<0.000) were obtained after excluding the five trisomy 21 children with elevated serum TSH (values >6.1 mU/L). Fourteen of 26 (54%) children with trisomy 21 had k(c) values of 0.20 to 0.60 (i.e., <-2SD). The values of kc positively correlated with body-mass index (BMI, R >0.302), serum creatinine (R >0.507), blood urea nitrogen (BUN, R >0.535) and albumin (R >0.446). CONCLUSIONS: Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.