Mitochondrial myopathy with lactic acidosis and deficient activity of muscle succinate cytochrome-c-oxidoreductase.

A male infant had severe muscular hypotonia from birth. Recurrent vomiting with dehydration and severe metabolic acidosis complicated the course. Elevated lactate (up to 12.3 mmol/l; n less than 2), pyruvate (0.4 mmol/l; n less than 0.05) and alanine levels were found in serum with an abnormal lactate/pyruvate ratio (greater than 30; n less than 15). In urine the concentrations of lactate, pyruvate, alanine and of several intermediates of the citric acid cycle were increased. In muscle, numerous disseminated "ragged red fibres" were found by light microscopy; muscle fibres were found to contain subsarcolemmal aggregates of mitochondria, lipid droplets and glycogen by electromicroscopical methods. Moreover, mitochondria with a typical circular arrangement of cristae were noticed. In liver homogenates normal activities of pyruvate carboxylase and pyruvate dehydrogenase complex were found; in liver mitochondria also succinate-cytochrome-c-oxidoreductase activity was normal. However, in muscle no succinate-cytochrome-c-oxidoreductase activity was detectable. The patient became increasingly lethargic and died because of sepsis at 5 months of age.

The clinical features of homozygous alpha 2(I) collagen deficient osteogenesis imperfecta.

The detailed clinical features and progress of a child with homozygous alpha 2(I) collagen deficiency are described. Clinically, the disease presents as severe progressive Sillence type III osteogenesis imperfecta. The main biochemical defect is the synthesis of an abnormal pro alpha 2(I) chain which does not associate with pro alpha 1(I) chains and therefore is not incorporated into triple helical trimers of type I procollagen which can be used to assemble collagen fibres.

Ultrastructure of the Arthus Phenomenon in muscle.

Specific blood-tissue barrier alterations were observed in a 2-year-old boy with a myopathic lesion in his muscle. Close by, degenerative changes were present in muscle fibers, three types of vascular abnormalities, i.e. increased vascular permeability, neutrophil aggregation, and damage of endothelium with thrombi formation, suggest that a process of vasculitis took place in the muscle of this patient. On the basis of current information it is not entirely clear whether this Arthus-like reaction observed in the primarily affected muscle represents a widespread vascular bed defect or whether it is the consequence of an additional secondary symptom possibly dependent upon muscle necrosis.

Mallory body-like inclusions in a hereditary congenital neuromuscular disease.

Subsequent to an earlier report on clinical and light microscopic data, peculiar Mallory body-like inclusions are described in muscle fibers of three genetically linked children. These Mallory body-like inclusions were unlike other well-defined intramuscular inclusions, such as nemaline, cytoplasmic, fingerprint, or sarcoplasmic bodies, but morphologically quite similar to hepatic Mallory bodies, because they were composed of three components: granular material and two types of filaments. Evidence is presented that these inclusions may contain desmin, the intermediate filament type characteristic of muscle. The exclusive appearance of these Mallory body-like inclusions in muscle biopsy specimens from three genetically related children of a large kinship emphasizes the uniqueness of these Mallory body-like inclusions in these muscle fibers as well as the special form of this congenital neuromuscular disorder.

A morphological study of non-Japanese congenital muscular dystrophy associated with cerebral lesions.

Clinical and morphological findings in five patients, three girls and two boys, afflicted with congenital muscular dystrophy (CMD) and cerebral lesions are reported. Four of these patients represented two pairs of siblings, and all patients had died in early infancy. Three of the patients had muscle hypotonia in early infancy, two siblings died with a necrotizing myopathy before neuromuscular symptoms became clinically apparent. Two siblings had intractable grand mal seizures, one other boy had polymicrogyria, and a single child had internal hydrocephalus. Muscle morphology in all patients was compatible with CMD, showing a necrotizing component in two male sibs. Electron microscopy of muscle only revealed non-specific ultrapathology. The association of CMD with cerebral lesions renders prognosis unfavourable. The data presented do not permit the delineation of a precise nosological form of cerebro-muscular disease but may comprise several entities. The association of CMD and cerebral lesions may often occur in families, apparently following an autosomal-recessive mode of inheritance. It may not be identical to the Fukuyama type of CMD, and it is definitely different from the "muscle, eye and brain disease" in Finnish children. It seems to be similar to CMD with cerebral lesions observed in non-Japanese siblings, but whether it is actually the same disease remains unclear. At least the association of CMD and cerebral lesions indicate an unfavourable clinical prognosis.

Pneumatosis intestinalis in children with leukaemia; report of three cases.

Three children with leukaemia (one with acute myeloid, two with acute lymphoblastic leukaemia) developed pneumatosis intestinalis during cytostatic treatment. The aetiology of pneumatosis intestinalis in these children could not be elucidated. Pneumatosis intestinalis may be caused by entry of gas into a bowel wall which is altered by steroid or cytostatic treatment. Otherwise, anaerobic bacteria may produce gas in the intestinal walls, therefore we treated all children with metronidazole.