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.