Carnitine deficiency and carnitine therapy in a patient with Rett syndrome

Background Rett syndrome can be diagnosed only clinically. Several biochemical abnormalities are known, but none of them is characteristic. To our knowledge only one study on carnitine deficiency and one case of successful carnitine therapy have been reported. Patient A five years old girl with normal milestones in the first months of life became retarded in the second year with muscle hypotonia of unknown cause and loss of known abilities. Later on recurrent washing movements of the hands, hyperventilation and microcephaly were observed and the diagnosis of Rett syndrome was established. Method A muscle biopsy was performed for the determination of enzymes of the respiratory chain and polarographic respirometry in permeabilized muscle fibres at the age of 3 1/2 years. Carnitine in plasma and urine was determined before and during a therapy with carnitine. Results The activities of some enzymes of the respiratory chain were slightly decreased as was oxygen consumption in the permeabilized muscle fibres. However muscle morphology and histochemistry were normal. With normal carnitine in the muscle plasma carnitine was clearly decreased but showed a normal ratio of acylcarnitine to free carnitine. Carnitine substitution was started at the age of 3 1/2 years with 75 mg/kg/day and was later increased to 150 mg/kg/day. The treatment showed not only a normalisation of plasma carnitine but also an improvement of physical activity, muscle hypotonia, communication and sleep time. A wash out for one month and resumption of therapy confirmed the efficacy of this regime. Conclusions The reason for the carnitine deficiency in the patient with Rett syndrome is not known. A primary carnitine deficiency is excluded by normal muscle carnitine. An explanation for the efficacy of the carnitine therapy is not known, although one could speculate that carnitine provides a transport system for acetyl groups, stimulates acetylcholine formation in the brain and in this way improves the disturbance of the cholinergic system.