ubiquinone and Acidosis

Mitochondrial acyl-CoA dehydrogenase 9 (ACAD9) deficiency is one of the common causes of respiratory chain complex I deficiency, which is characterized by cardiomyopathy, lactic acidemia, and muscle weakness. Infantile cardiomyopathy is the most common phenotype and is usually lethal by the age of 5 years. Riboflavin treatment is known to be effective in ~65% of the patients; however, the remaining are unresponsive to riboflavin and are in need of additional treatment measures. In this report, we describe a patient with ACAD9 deficiency who developed progressive cardiomyopathy at 8 months of age. As the patient's left ventricular ejection fraction (LVEF) kept decreasing to 45.4% at 1 year 8 months, sodium pyruvate treatment was introduced together with a beta-blocker and coenzyme Q10. This resulted in a steady improvement, with full and sustained normalization of cardiac function without riboflavin. The therapy, therefore, might be a useful addition for the treatment of ACAD9 deficiency.

Topics: Acidosis; Acyl-CoA Dehydrogenase; Acyl-CoA Dehydrogenases; Adrenergic beta-Antagonists; Amino Acid Metabolism, Inborn Errors; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Carvedilol; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Mitochondrial Diseases; Muscle Weakness; Prognosis; Pyruvates; Ubiquinone; Vitamins

evaluate the psychomotor evolution of a child with Multiple acyl-CoA dehydrogenase deficiency after treatment with L-carnitine, ubiquinone and riboflavin.. an assessment of psychomotor development was performed before the start of farmacological treatment using the Assessment Scale of Mental Development Griffiths (GMDS-R, 0-2 years). The same assessment was performed after a month and after six months of treatment to evaluate the possible benefits of treatment.. we noticed a quick and dramatic improvement in muscular tone and motor performances after pharmacological treatment. We also observed a substantial improvement in the personal/social and hearing/language areas, suggesting the presence of intellectual/cognitive improvement. The clinical improvement correlated with the biochemical response.. In our patient early therapy resulted in a optimal response in psychomotor development, motor function and muscole hypotonia. Evaluation with GMDS-R, a simple, non-invasive and multidimensional tool, represents a useful instrument to monitor the clinical response to treatment.

Topics: Acidosis; Acyl-CoA Dehydrogenase; Amino Acid Metabolism, Inborn Errors; Carnitine; Child Development; Hearing; Humans; Hypoglycemia; Infant; Language Development; Male; Muscle Hypotonia; Muscle, Skeletal; Neuropsychological Tests; Psychomotor Performance; Riboflavin; Social Behavior; Tandem Mass Spectrometry; Ubiquinone; Vitamins

3-Methylglutaconic aciduria is an organic aciduria with diverse phenotypic presentations. In more than half of the cases it is a 'neurologic or silent organic aciduria', and, except for one subtype, the biochemical defect is unknown. This report describes 10 new patients. Four of them presented with early global neurologic involvement and arrested development. They rapidly became demented, developed myoclonus or tonic-clonic seizures, spastic quadriplegia, deafness and blindness, and died. Three had acidosis and hypoglycemia neonatally; later, myoclonus and deafness, and eventually severe mental retardation and spastic quadriplegia developed. One patient died. In three children who presented with sudden onset of extrapyramidal tract symptoms, with or without optic atrophy, the clinical presentation was significantly different from that described either for 'unspecified' type or for Costeff syndrome. All three patients showed clinical improvement soon after treatment with coenzyme Q.

Topics: Acidosis; Basal Ganglia Diseases; Child, Preschool; Female; Glutarates; Humans; Infant; Male; Metabolism, Inborn Errors; Nervous System Diseases; Phenotype; Ubiquinone

A patient is presented who had therapy-resistant epileptic seizures from the 7th day of life. Examination at the age of 17 months revealed a mentally retarded boy with epileptic seizures, generalised myoclonic contractions, and abnormal ocular movements. A cerebral CT scan showed central and cortical atrophy. Lactate levels in serum, cerebrospinal fluid and urine were elevated, the pyruvate level was raised in serum. A quadriceps muscle biopsy revealed aspecific morphologic signs of a myopathy. Biochemical analysis showed decreased substrate oxidation rates in the mitochondria associated with low rates of ATP production. Total and free carnitine levels were decreased. Investigation of the respiratory chain revealed a defect in the proximal part of respiratory chain involving the region of coenzyme Q. Based on clinical and chemical data it is likely that the patient is suffering from a multi-system disorder.

Topics: Acidosis; Adenosine Triphosphate; Brain Diseases; Epilepsy; Humans; Infant; Intellectual Disability; Lactates; Male; Mitochondria, Muscle; Muscle Spasticity; Myoclonus; NAD; Nystagmus, Pathologic; Oxidation-Reduction; Pyruvates; Ubiquinone