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Background:Very few mitochondrial myopathies have been described in horses.Objective:To examine the ultrastructure of muscle mitochondria in equine cases of myopathy of unknown origin.Materials &methods:Biopsies of vastus lateralisof the Musculus quadriceps femoriswere taken predominantly immediately post mortemand processed for transmission electron microscopy. As a result, electron micrographs of 90 horses in total were available for analysis comprising 4 control horses, 16 horses suffering from myopathy and 70 otherwise diseased horses.Results:Following a thorough clinical and laboratory work-up, four out of five patients that did not fit into the usual algorithm to detect known causes of myopathy showed ultrastructural mitochondrial alterations. Small mitochondria with zones with complete disruption of cristae associated with lactic acidemia were detected in a 17-year-old pony mare, extremely long and slender mitochondria with longitudinal cristae in a 5-year-old Quarter horse stallion, a mixture of irregular extremely large mitochondria (measuring 2500 by 800 nm) next to smaller ones in an 8-year-old Hanoverian mare and round mitochondria with only few cristae in a 11-year-old pony gelding. It remains uncertain whether the subsarcolemmal mitochondrial accumulations observed in the fifth patient have any pathological significance.Conclusions:Ultrastructural alterations in mitochondria were detected in at least four horses. To conclude that these are due to mitochondrial dysfuntions, biochemical tests should be performed.Practical applications:The possibility of a mitochondrial myopathy should be included in the differential diagnosis of muscle weakness.

Heterozygous mutations in STXBP1, encoding the syntaxin binding protein 1, have recently been identified in Ohtahara syndrome, an epileptic encephalopathy with very early onset. In order to explore the phenotypic spectrum associated with STXBP1mutations, we analyzed a cohort of patients with unexplained early-onset epileptic encephalopathies.

Combined OXPHOS-system enzyme deficiencies are observed in approximately 25% of all OXPHOS-system disturbances. Of these, combined complex I and III deficiency is relatively scarce. So far, only mtDNA and thymidine phosphorylase (TP) mutations have been associated with combined OXPHOS-system disturbances. In this report we show, for the first time, that a nuclear gene mutation in a structural, nuclear encoded complex I gene is associated with combined complex I and III deficiency. After our initial report we describe mutations in the NDUFS4 gene of complex I in two additional patients. The first mutation is a deletion of G at position 289 or 290. Amino acid 96 changes from a tryptophan to a stop codon. The mutation was found homozygous in the patient; both parents are heterozygous for the mutation. The second mutation is a transition from C to T at cDNA position 316. Codon is changed from CGA (arginine) to TGA (stop). The patient is homozygous for the mutation; both parents are heterozygous. Both mutations in the NDUFS4 gene led to a premature stop in Leigh-like patients with an early lethal phenotype. We hypothesise that the structural integrity of the OXPHOS system, in mammal supermolecular structures, may be responsible for the observed biochemical features.

We screened 41 patients with undiagnosed encephalomyopathies and cytochrome coxidase (COX) deficiency for mutations in two COX assembly genes, SURF‐1and SCO2;6 patients had mutations in SURF‐1and 3 had mutations in SCO2. All of the mutations in SURF‐1were small‐scale rearrangements (deletions/insertions); 3 patients were homozygotes and the other 3 were compound heterozygotes. All patients with SCO2mutations were compound heterozygotes for nonsense or missense mutations. All of the patients with mutations in SURF‐1had Leigh syndrome, whereas the 3 patients with SCO2mutations had a combination of encephalopathy and hypertrophic cardiomyopathy, and the neuropathology did not show the typical features of Leigh syndrome. In patients with SCO2mutations, onset was earlier and the clinical course and progression to death more rapid than in patients with SURF‐1mutations. In addition, biochemical and morphological studies showed that the COX deficiency was more severe in patients with SCO2mutations. Immunohistochemical studies suggested that SURF‐1mutations result in similarly reduced levels of mitochondrial‐encoded and nuclear‐encoded COX subunits, whereas SCO2mutations affected mitochondrial‐encoded subunits to a greater degree. We conclude that patients with mutations in SURF‐1and SCO2genes have distinct phenotypes despite the common biochemical defect of COX activity. Ann Neurol 2000;47:589–595

ABSTRACT: The devastating nature of a pyruvate carboxylase deficiency is underscored by the uniformly fatal outcome of the neonatal (French) type and the severely disabling and ultimately fatal outcome of the infantile (North American) type. We report a ?-y-old girl with metabolic and biochemical features of the North American phenotype. Remarkably, the clinical course has been benign with preservations of motor and mental abilities. The residual enzyme activity in cultured skin fibroblast homogenates was 1.8% and cross-reacting material was present in normal abundance and electrophoretic mobility. She has had several episodes of metabolic acidosis with elevated lactate, pyruvate, alanine, ß-hydroxybutyrate, acetoacetate, lysine, and proline values, and undetectably low aspartate concentrations. These crises have been managed by rehydration and bicarbonate therapy. We are unable to provide a satisfactory explanation for the uniquely benign clinical course that has been experienced by this patient.

Summary Four cases of large suprasellar arachnoid cysts in children are described. The authors propose a large fenestration into the lateral ventricles and into the basal cisterns as the treatment of choice. A specific multipurpose cerebral endoscope has been designed by the first author. The endoscopic technique with different instruments and with the use of a laser is illustrated. Results and complications are discussed.

four patients with spastic dystonia from two of our 35 lhon families. Magnetic resonance imaging revealed signal alterations of globus pallidus, putamen, internal capsula, and substantia nigra. Neuropathological findings in one of the patients with dystonia are described. Each of the dystonia families carries a different mtDNA mutation; one at np 3460 and one at np 11778. Periventricular multiple sclerosis-like white matter lesions were observed in one individual from a third family with the mtDNA 3460 mutation. Neurological disorders are probably underestimated in association with lhon.

Pyruvate carboxylase (PC) deficiency is a rare metabolic disorder in infants and children, most frequently with fatal outcome. Its prenatal diagnosis by radiometric assay in cultured amniocytes has previously been reported. We present and discuss the prenatal diagnosis of PC deficiency by direct measurement of PC activity in chorionic villi, in two subsequent pregnancies in a family who previously lost a child affected by PC deficiency. In the next pregnancy PC was unmeasurably low in chorionic villi whereas in control samples its activity was between 0·8 and 3·3 nmol min−1mg protein−1. Following elective termination of the pregnancy PC was shown to be totally inactive in post‐mortem fetal liver. In the most recent pregnancy of the proband's mother PC was normally active in the chorionic villi. The product of this pregnancy was a normal boy. Copyright © 1998 John Wiley & Sons, Ltd.