Background: The most common nuclear-coded mitochondrial diseases are due to mutations in the polymerase gamma (POLG) gene. POLG1-associated epilepsy (often characterized by an occipital zone of origin of seizures) is characterized by intermittent critical exacerbations, which often result in a non-convulsive status epilepticus and are mostly refractory to treatment. At the functional level, it is unclear whether the exacerbation is primarily due to epileptic neuronal overactivity or primarily to a disturbed energy metabolism.

Background: Marinesco-Sjogren syndrome is an autosomal recessive cerebellar ataxia, characterised by cerebellar ataxia, myopathy, cataracts and intellectual disability, due to mutations in the SIL1 gene.Methods: The clinical features and two novel SIL1 mutations of four Dutch patients with Marinesco-Sjogren syndrome are described and compared to the literature on genetically proven Marinesco-Sjogren patients.Results: The core phenotype of this syndrome appears homogeneous, but: [1] cataract can develop later than the motor and cognitive signs; [2] myopathy is an early feature that seems progressive during the course of the disease; [3] serum creatine kinase is normal or only mildly elevated; [4] peripheral neuropathy is absent; and [5] a variable degree of intellectual disability is present in most Marinesco-Sjogren patients.Conclusions: Because the late appearance of some hallmarks and the uncertainty as to whether incomplete phenotypes occur, SIL1 mutation analysis is helpful early in the diagnostic work-up of children with suspected inherited ataxias. (C) 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Aims: The female is the first child of healthy, non-consanguineous German parents. From the age of two years failure to thrive and a pre-disposition for infections was observed. At the age of six years sensorineural hearing loss and hypoparathyreoidis occurred. The patient was referred to us at the age of 7.4 years for psychosomatic therapy, having been diagnosed with interaction problems within the family, refusal to eat and vomiting. Upon admission significant dystrophy was noted. Elektrolyte imbalance, hypoglycemia and lactic acidemia occured upon nasogastral tube feeding with a high-caloric diet. Neurological examination revealed a myopathic facies, mild ptosis, external ophtalmoplegia, generalized muscular hypotonia, ataxia, dysmetria and intermittent tremor. ECG and echocardiography were unremarkable.

Albuterol, a selective beta-adrenergic agonist, has been used experimentally in combination with exercise therapy in a few inherited neuromuscular disorders to increase muscle strength and muscle volume . We report on a 9-year-old boy with central core disease and mitochondrial dysfunction due to compound heterozygous RYR1 mutations receiving albuterol treatment for 1 year. Throughout the period of albuterol administration, the patient underwent an aerobic exercise regime of training sessions three times a week that lasted 20 min each. No side effects of albuterol use were seen. Significant clinical progress, including self care, sitting up, raising arms above the shoulders, independent feeding, and better speech and writing were observed compared with minimal development of these abilities in the previous years on physiotherapy. Improved forced expiratory volume in 1 s (FEV1) score was detected and increased muscle strength was noted: progress was measured using various functional tests and assessment scales. The only complication observed was a mild progression of the joint contractures, possibly due to an unbalance between the flexor and extensor musculature. In general, in this pilot study in a complex case of metabolic myopathy our patient has shown promising results following albuterol treatment and aerobic exercise therapy.

A higher incidence of major depression has been described in adults with a primary oxidative phosphorylation disease. Intriguingly however, not all patients carrying the same mutation develop symptoms of major depression, pointing out the significance of the interplay of genetic and non-genetic factors in the etiology. In a series of paediatric patients evaluated for mitochondrial dysfunction, out of 35 children with a biochemically and genetically confirmed mitochondrial disorder, we identified five cases presenting with major depression prior to the diagnosis. The patients were diagnosed respectively with mutations in MTTK, MTND1, POLG1, PDHA1 and the common 4977 bp mtDNA deletion. Besides cerebral lactic acidemia protein and glucose concentrations, immunoglobins, anti-gangliosides and neurotransmitters were normal. No significant difference could be confirmed in the disease progression or the quality of life, compared to the other, genetically confirmed mitochondrial patients. In three out of our five patients a significant stress life event was confirmed. We propose the abnormal central nervous system energy metabolism as the underlying cause of the mood disorder in our paediatric patients. Exploring the genetic etiology in children with mitochondrial dysfunction and depression is essential both for safe medication and adequate counselling.

In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of Leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid.