Lymphocyte respiration in children with Trisomy 21

Abstract

Doc number: 193

Abstract

Background: This study measured lymphocyte mitochondrial O₂ 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. [O₂ ] 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, [O₂ ] declined linearly with time, confirming the zero-order kinetics of O₂ conversion to H₂ O by cytochrome oxidase. The rate of respiration (k , in μM O₂ min^-1 ), thus, was the negative of the slope of [O₂ ] vs. time. Cyanide inhibited O₂ 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 k_c (in μM O₂ per min per 10⁷ 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 k_c 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.