Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coenzyme Q(10) is a mobile lipophilic electron carrier located in the inner mitochondrial membrane. Defects of coenzyme Q(10) biosynthesis represent one of the few treatable mitochondrial diseases. We genotyped a patient with primary coenzyme Q(10) deficiency who presented with neonatal lactic acidosis and later developed multisytem disease including intractable seizures, global developmental delay, hypertrophic cardiomyopathy, and renal tubular dysfunction. Cultured skin fibroblasts from the patient had a coenzyme Q(10) biosynthetic rate of 11% of normal controls and accumulated an abnormal metabolite that we believe to be a biosynthetic intermediate. In view of the rarity of coenzyme Q(10) deficiency, we hypothesized that the disease-causing gene might lie in a region of ancestral homozygosity by descent. Data from an Illumina HumanHap550 array were analyzed with BeadStudio software. Sixteen regions of homozygosity >1.5 Mb were identified in the affected infant. Two of these regions included the loci of two of 16 candidate genes implicated in human coenzyme Q(10) biosynthesis. Sequence analysis demonstrated a homozygous stop mutation affecting a highly conserved residue of COQ9, leading to the truncation of 75 amino acids. Site-directed mutagenesis targeting the equivalent residue in the yeast Saccharomyces cerevisiae abolished respiratory growth.
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PMID:A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. 1937 58

Coenzyme Q10 (CoQ10) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ10 synthesis are usually associated with the impaired function of CoQ10-dependent complexes I, II and III. The recessively transmitted CoQ10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ10 biosynthesis. To date, mutations in COQ1 (PDSS1 and PDSS2), COQ2, COQ4, COQ6, COQ7, COQ8A/ADCK3, COQ8B/ADCK4, and COQ9 genes have been identified in patients with primary form of CoQ10 deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ10 deficiency.
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PMID:Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency. 2854 Jan 86

Background Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation. Case presentation A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9. A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage. Conclusions We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.
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PMID:A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation. 3182 Nov 67