Compulsory hyperventilation and hypocapnia of patients with Leigh syndromeassociated with SURF1 gene mutations as a cause of low serum bicarbonates

Experimental data show that elevation of intracellular pH leads to severe l esions of brain cells. Acidification of intracellular fluid by accumulation of lactate may compensate the effect of respiratory alkalosis. Increased s erum pH, and low PCO2, associated with hyperlactataemia (sometimes incorrec tly called 'acidosis') have been reported in children with Leigh syndrome ( LS). The aim of the study was to determine whether respiratory alkalosis is char acteristic of patients with LS due to SURF1 mutations. All venous blood gas data (88 samples) of 18 spontaneously breathing LS patients with recently established SURF1 mutations, hospitalized during 1986-2000, were retrospect ively reviewed. The data of an affected boy who survived on a respirator fo r more than 3 months (79 daily samples) were analysed separately. In spontaneously breathing patients, the data indicated that the patients h ad compensated or partially compensated respiratory alkalosis (pH 7.388 +/- 0.060, PCO2 29.2 +/- 5.7 mmHg, HCO3- 17.4 +/- 3.0 mmol/L, BE -6.7 +/- 3.2 mmol/L). Bicarbonate excretion was detected in urine of two examined LS cas es in spite of decreased serum HCO3-. In the affected child maintained on a respirator, simple manipulation of the inspired CO2 tension to establish a normal pressure of 35-45 mmHg automatically caused an increase of serum HC O3- concentration to a normal value of 26.3 +/- 2.9 mmol/L (and BE to +2.2 +/- 3.1 mmol/L), in spite of cytochrome oxidase (COX) deficiency due to a c onfirmed SURF1 mutation. We suggest that respiratory alkalosis (hypocapnia) of Leigh syndrome patien ts with SURF1 mutations results from compulsory hyperventilation and specul ate that hypocapnia may contribute to Leigh-like brain damage in the SURF1- deficient patients as well as in other patients presenting with Leigh-like syndrome. The supposition that accumulation of lactate may protect the brai n of LS patients from alkalosis-related damage requires further study. Avoi dance of any factors stimulating hyperventilation of LS patients and cautio n when attempting to correct low plasma bicarbonate are suggested.