Pyruvate dehydrogenase deficiency presenting as dystonia and responding to levodopa' SIR-We read with much interest the recent article of Head et al., 1 in which they described two cases of pyruvate dehydrogenase (PDH) deficiency presenting during childhood with dystonia. We fully agree with the authors' findings as we have also encountered two brothers with confirmed PDH deficiency (partial defect in E1 subunit) who presented to us with severe dystonia, which remained the prominent clinical sign.The elder brother presented at the age of 3 months when parents noted attacks of chin tremors and states of sudden unresponsiveness, later confirmed to be of epileptic origin. He was first examined at the age of 9 months when psychomotor delay was found with severe head lag, dyskinetic posturing with increased muscle tone, and exaggerated deep tendon reflexes. On a few occasions, the investigations revealed increased plasma lactate levels (up to 6.5mmol/l) while lactate level in cerebrospinal fluid (CSF) was 1.8mmol/l. Urinary organic acid and plasma aminoacid profiles were normal. Brain magnetic resonance imaging (MRI) revealed diffuse brain atrophy, while electromyography and nerve conduction study were normal as well as visual evoked potentials and electroretinography. Somatosensory evoked potentials demonstrated diminished amplitudes of cortical responses after median nerve stimulation. Electroencephalogram (EEG) was abnormal and revealed diffuse background activity, slowing and frequent generalized discharges of fast spikes and spike and wave complexes, sometimes accompanied by myoclonic seizures during sleep. Muscle biopsy specimen was performed at Clinical Genetics Centre, Metabolic Division in Nijmegen, the Netherlands and revealed decreased activities of PDH complex (1.9mU per mg protein; control range: 2.7-8.2mU per mg protein), and especially E1 subunit (0.046 -control range: 0.083 -0.25mU per mg protein), while fibroblast culture revealed normal basal and total PDH complex activities, thus, reflecting tissue-specific expression, the phenomenon being frequently encountered in many patients with PDH deficiency. The patient is now 15 years old and is cared for in an institution, is quite emaciated, however he still has some preservation of psychosocial contact, but is bed-ridden with severe dystonic and spastic posturing. He has occasional generalized myoclonic seizures despite regular valproate and vigabatrin treatment.His younger brother presented to us at the age of 4 months because his parents noted similar clinical signs to those of his elder sibling: chin tremors, hand fisting, and unusual posturing of feet and hands. On examination, poor eye-to-eye contact was noted with slightly decreased muscle tone, especially in the axial muscles, and dystonia of feet and hands with dystonic facial expressions. At age 7 months, the parents sought a second opinion from the Institute of Child Health, London, UK, where it was confirmed that the younger brother probably had a similar disorder to his elder brother. However...
