Rett syndrome: a mitochondrial disease?

Six girls between 2 years 9 months and 15 years of age with Rett syndrome were thoroughly investigated. Blood ammonia levels varied between 42 and 123 mumol/L, and serum lactate concentration was slightly elevated in two girls. Electroencephalograms showed a dysrhythmic pattern during wakefulness; during drowsiness and light sleep, bilateral bursts of spike or multispike-and-wave activity were seen in all but the oldest girl. In one of the younger girls, slight cortical atrophy was found on computed tomographic scan. Muscle biopsy was performed on all girls, and electron microscopy revealed abnormal mitochondria. Physical signs such as somatic hypotrophy with extremely small muscle mass, and unsatisfactory weight gain in spite of good appetite are found in Rett syndrome. These attributes, as well as reports of ornithine carbamoyltransferase deficiency, may support a mitochondrial dysfunction. The mitochondrial changes indicate either a mitochondrial mutation or more probably an X-borne modulator gene mutation. Another genetic possibility discussed is the "metabolic interference" of an X-borne allele. Further delineation of such mitochondrial changes may clarify the causal metabolic defect in Rett syndrome.

Intervertebral discitis in childhood.

Many paediatricians are unaware of the disease entity of discitis, which must be included in the differential diagnosis of several acute and subacute diseases of infancy and childhood. In order to draw attention to this disorder, three Swedish and two Arabic children, aged from 9 months to 3 years, are jointly presented. The onset of symptoms was 2-4 weeks prior to admission. The clinical diagnosis was verified by plain X-ray of the spine and bone scanning. Two of the children had low grade fevers. The erythrocyte sedimentation rates were moderately elevated, while white blood cell counts were normal or slightly increased. Blood cultures were negative. The children were treated with immobilization, and three of them received antibiotics. Full recovery was achieved in all children after 1-2 months. The diagnostic procedure and the rationale of using or not using antibiotic treatment is discussed.

Abnormal mitochondria in the Rett syndrome.

Two girls with Rett syndrome were investigated including muscle biopsy. The electron microscopy study revealed abnormally swollen and dumb-bell shaped mitochondria. Based on the findings of mitochondrial changes it can be assumed that such changes are due to a mitochondrial mutation steered by an X-borne gene mutation. As a result and because the mitochondrial DNA is maternally inherited, the male zygote may not be implanted or it will proceed to an early embryonal death. The mitochondrial changes with the ensuing effects may be the basic cause of the syndrome.