ubiquinone and Leigh-Disease

The genetic causes of Leigh syndrome are heterogeneous, with a poor correlation between the phenotype and genotype. Here, we present a patient with an NDUFS4 mutation to expand the clinical and biochemical spectrum of the disease. A combined defect in the CoQ, PDH and RCC activities in our patient was due to an inappropriate assembly of the RCC complex I (CI), which was confirmed using Blue-Native polyacrylamide gel electrophoresis (BN-PAGE) analysis. Targeted exome sequencing analysis allowed for the genetic diagnosis of this patient. We reviewed 198 patients with 24 different genetic defects causing RCC I deficiency and compared them to 22 NDUFS4 patients. We concluded that NDUFS4-related Leigh syndrome is invariably linked to an early onset severe phenotype that results in early death. Some data, including the clinical phenotype, neuroimaging and biochemical findings, can guide the genetic study in patients with RCC I deficiency.

Topics: Electron Transport Complex I; Electrophoresis, Polyacrylamide Gel; Female; Humans; Infant, Newborn; Leigh Disease; NADH Dehydrogenase; Ubiquinone

Mitochondrial disorders encompass any medical specialty and affect patients at any age. Likewise, the spectrum of clinical and genetic signatures of these disorders is ample, making a precise diagnosis difficult. We will report some of the major clinical phenotypes observed in infancy, their underlining molecular features, and will propose an approach to reach a more complete diagnosis.

Topics: Brain; Coenzymes; DNA, Mitochondrial; Electron Transport Complex I; Humans; Infant; Leigh Disease; Mitochondrial Diseases; Mutation; Succinate-CoA Ligases; Ubiquinone

Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results.. A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6 months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease.. Ten consecutive children, ages 1-13 years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints--Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module--demonstrated statistically significant improvement (p<0.05). In addition, all children had an improvement of one class on the Movement Disorder-Childhood Rating Scale. No significant drug-related adverse events were recorded.. In comparison to the natural history of Leigh syndrome, EPI-743 improves clinical outcomes in children with genetically confirmed Leigh syndrome.

Topics: Adolescent; Child; Child, Preschool; Compassionate Use Trials; Disease Progression; Drug Administration Schedule; Female; Humans; Infant; Leigh Disease; Male; Mitochondria; Psychomotor Performance; Quality of Life; Severity of Illness Index; Ubiquinone

Leigh syndrome, the most common mitochondrial syndrome in pediatrics, has diverse clinical manifestations and is genetically heterogeneous. Pathogenic mutations in more than 75 genes of two genomes (mitochondrial and nuclear) have been identified. PDHA1 encoding the E1 alpha subunit is an X-chromosome gene whose mutations cause pyruvate dehydrogenase complex deficiency.. Here, we have described a 12-year-old boy with lethal neuropathy who almost died of a sudden loss of breathing and successive cardiac arrest. Extracorporeal membrane oxygenation rescued his life. His diagnosis was corrected from Guillain-Barré syndrome to Leigh syndrome 1 month later by clinical exome sequencing. Furthermore, we used software to predict the protein structure caused by frameshift mutations. We treated the boy with vitamin B1, coenzyme Q10, and a ketogenic diet.. A PDHA1 mutation (NM_000284.4:c.1167_1170del) was identified as the underlying cause. The amino acid mutation was p.Ser390LysfsTer33. Moreover, the protein structure prediction results suggested that the protein structure has changed. The parents of the child were negative, so the mutation was de novo. The comprehensive assessment of the mutation was pathogenic. His condition gradually improved after receiving treatment.. This case suggests that gene detection should be popularized to improve diagnosis accuracy, especially in developing countries such as China.

Topics: Child; Diet, Ketogenic; Frameshift Mutation; Humans; Leigh Disease; Male; Pyruvate Dehydrogenase (Lipoamide); Thiamine; Ubiquinone; Vitamins

Topics: Baclofen; Carnitine; Child, Preschool; Diagnosis, Differential; Diet, Ketogenic; Humans; Leigh Disease; Male; Muscle Relaxants, Central; Muscle Weakness; Pyruvate Dehydrogenase Complex Deficiency Disease; Ubiquinone; Vitamins

Leigh syndrome is one of the most common childhood-onset neurometabolic disorders resulting from a primary oxidative phosphorylation dysfunction and affecting mostly brain tissues. Ndufs4

Topics: Adenosine Triphosphate; Animals; Electron Transport Complex I; Flavoproteins; Glycolysis; Leigh Disease; Male; Metabolomics; Mice; Mice, Knockout; Mitochondrial Diseases; Models, Animal; Muscle, Skeletal; Oxidation-Reduction; Oxidative Phosphorylation; Ubiquinone

The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that

Topics: Animals; Brain; Calcium; Electron Transport Complex III; Leigh Disease; Liver; Male; Membrane Potential, Mitochondrial; Metalloproteases; Mice; Mice, Knockout; Mitochondria; Mitochondrial Encephalomyopathies; Mitochondrial Proteins; Muscle, Skeletal; Reactive Oxygen Species; Ubiquinone

COQ4 mutations have recently been shown to cause a broad spectrum of mitochondrial disorders in association with CoQ10 deficiency. Herein, we report the clinical phenotype, in silico and biochemical analyses, and intervention for a novel c.370 G > A (p.G124S) COQ4 mutation in a Chinese family. This mutation is exclusively present in the East Asian population (allele frequency of ~0.001). The homozygous mutation caused CoQ10 deficiency-associated Leigh syndrome with an onset at 1-2 months of age, presenting as respiratory distress, lactic acidosis, dystonia, seizures, failure to thrive, and detectable lesions in the midbrain and basal ganglia. No renal impairment was involved. The levels of CoQ10 and mitochondrial respiratory chain complex (C) II + III activity were clearly lower in cultured fibroblasts derived from the patient than in those from unaffected carriers; the decreased CII + III activity could be increased by CoQ10 treatment. Follow-up studies suggested that our patient benefitted from the oral supplementation of CoQ10, which allowed her to maintain a relatively stable health status. Based on the genetic testing, preimplantation and prenatal diagnoses were performed, confirming that the next offspring of this family was unaffected. Our cases expand the phenotypic spectrum of COQ4 mutations and the genotypic spectrum of Leigh syndrome.

Topics: Asian People; Ataxia; Child, Preschool; Computer Simulation; Female; Fibroblasts; Genetic Testing; Heterozygote; Homozygote; Humans; Infant; Leigh Disease; Male; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Muscle Weakness; Mutation; Phenotype; Ubiquinone

Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating.. At 5months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings. Sequence analysis for mitochondrial DNA revealed a T10158C mutation in the mitochondrial encoded ND3 gene in complex I.. At 8months, succinate was prescribed expected to restore the electron transport chain system. After that her condition got worse and succinate was discontinued. Subsequent administration of EPI-743 improved her eye movement, fine motor movements of the extremities, and bowel movement. She is now 5years old. Although brain atrophy has progressed, she has still respiratory free time.. Our patient showed visible improvement with EPI-743 treatment and the only patient surviving after 4years. There is a possibility that EPI-743 is modifying the natural course of the syndrome.

Topics: Antioxidants; Brain; Child, Preschool; Disease Progression; Electron Transport Complex I; Female; Humans; Lactic Acid; Leigh Disease; Respiration, Artificial; Ubiquinone

Primary CoQ

Topics: Acidosis, Lactic; Ataxia; Autopsy; Exome Sequencing; Female; Humans; Infant, Newborn; Leigh Disease; Male; Mitochondrial Diseases; Muscle Weakness; Mutation; Pregnancy; Siblings; Ubiquinone

Mitochondrial diseases are a group of clinically heterogeneous disorders that can be difficult to diagnose. We report a two and a half year old girl with clinical symptoms compatible with Leigh disease but with no definitive diagnosis. Using next generation sequencing we found that mutation 3697G>A was responsible for the patient's clinical symptoms. Corroboration was performed via segregation analysis in mother and sister and by evolutionary analysis that showed that the mutation is located in a highly conserved region across a wide range of species. Functional analyses corroborated the mutation effect and indicated that the pathophysiological alterations were partially restored by Coenzyme Q10. In addition, we proposed that the presence of the mutation at high frequencies causes the phenotype in the patient, while other family members with intermediate levels of heteroplasmy are symptoms-free.

Topics: Child, Preschool; DNA, Mitochondrial; Female; High-Throughput Nucleotide Sequencing; Humans; Leigh Disease; NADH Dehydrogenase; Point Mutation; Ubiquinone

Topics: Acidosis, Lactic; Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Cells, Cultured; Child; Child, Preschool; DNA, Mitochondrial; Female; Fibroblasts; Humans; Infant; Infant, Newborn; Leigh Disease; Male; Microtubule-Associated Proteins; Middle Aged; Mitochondrial Dynamics; Mitochondrial Membrane Transport Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Mitophagy; Mutation; Neurology; Ubiquinone; Young Adult

The Leigh syndrome (LS), characterized by psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure, is one of the most severe mitochondrial diseases. In the majority of cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A was found to relate to the severe phenotype of the Leigh syndrome. Here, we describe the first Chinese Leigh syndrome pedigree with this mutation. The proband had the characteristic brain lesions of the Leigh syndrome and presented a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband, as well as her unaffected brother, have a high mutant load in the ND3 gene, compared to their mother. Following one‑year treatment with the coenzyme Q10, an obvious improvement in clinical features was observed by magnetic resonance imaging (MRI) in the proband. Our study and previous reports highlight the variability of phenotypic expression of the m.10197 G>A mutation, and suggest that pathogenesis of the syndrome may be affected by a number of factors. This is the first report on successful treatment of an LS patient carrying the mutation m.10197 G>A with the coenzyme Q10, indicating that Q10 may attenuate the mitochondrial dysfunctions caused by the m.10197 G>A mutation.

Topics: Adolescent; Amino Acid Sequence; Asian People; Biopsy; Brain; Child; Child, Preschool; China; DNA Mutational Analysis; DNA, Mitochondrial; Female; Haplotypes; Heterozygote; Humans; Infant; Infant, Newborn; Leigh Disease; Magnetic Resonance Imaging; Male; Muscle, Skeletal; Mutation; NADH Dehydrogenase; Pedigree; Treatment Outcome; Ubiquinone

Mitochondrial diseases are notoriously difficult to diagnose due to extreme locus and allelic heterogeneity, with both nuclear and mitochondrial genomes potentially liable. Using exome sequencing we demonstrate the ability to rapidly and cost effectively evaluate both the nuclear and mitochondrial genomes to obtain a molecular diagnosis for four patients with three distinct mitochondrial disorders. One patient was found to have Leigh syndrome due to a mutation in MT-ATP6, two affected siblings were discovered to be compound heterozygous for mutations in the NDUFV1 gene, which causes mitochondrial complex I deficiency, and one patient was found to have coenzyme Q10 deficiency due to compound heterozygous mutations in COQ2. In all cases conventional diagnostic testing failed to identify a molecular diagnosis. We suggest that additional studies should be conducted to evaluate exome sequencing as a primary diagnostic test for mitochondrial diseases, including those due to mtDNA mutations.

Topics: Ataxia; Child, Preschool; Electron Transport Complex I; Exome; Female; Genetic Variation; Genome, Mitochondrial; Heterozygote; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Leigh Disease; Mitochondria; Mitochondrial Diseases; Molecular Diagnostic Techniques; Muscle Weakness; Pedigree; Sequence Analysis, DNA; Sequence Analysis, RNA; Ubiquinone

The multi-organ involvement of mitochondrial diseases means that patients are likely to be more vulnerable to sleep disturbances. We aimed to assess if early recognition and treatment of obstructive sleep apnea (OSA) in patients with Leigh disease may influence primary disease outcome.. We describe a case of adult-onset Leigh disease presenting as severe brainstem encephalopathy of subacute onset. Based on the clinical symptoms that developed after the appearance of the neurological disease, an attended overnight polysomnography examination was performed.. A marked clinical recovery was seen after administration of high doses of thiamine, coenzyme Q, L-carnitine, and vitamins C and E, combined with effective treatment with continuous positive airway pressure for the underlying severe obstructive sleep apnea (OSA). The latter condition was diagnosed on the basis of suggestive symptoms that appeared a few weeks before the establishment of the neurological disease. The improvement in the neurological disease (based on clinical and brain MRI features) with the appropriate medical treatment also resulted in a significant improvement in the OSA.. Early recognition and treatment of sleep apnea may not only improve sleep and overall quality of life but also ameliorate the deleterious effects of nocturnal desaturations on the neurological features. This may be crucial for disease outcome when added to the generally advised pharmacological therapy.

Topics: Adult; Brain; Carnitine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Leigh Disease; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Neurologic Examination; Polysomnography; Sleep Apnea, Obstructive; Thiamine; Ubiquinone; Vitamin D; Vitamin E

In this study, we investigated the pathogenicity of a homozygous Asp446Asn mutation in the NDUFS2 gene of a patient with a mitochondrial respiratory chain complex I deficiency. The clinical, biochemical, and genetic features of the NDUFS2 patient were compared with those of 4 patients with previously identified NDUFS2 mutations. All 5 patients presented with Leigh syndrome. In addition, 3 out of 5 showed hypertrophic cardiomyopathy. Complex I amounts in the patient carrying the Asp446Asn mutation were normal, while the complex I activity was strongly reduced, showing that the NDUFS2 mutation affects complex I enzymatic function. By contrast, the 4 other NDUFS2 patients showed both a reduced amount and activity of complex I. The enzymatic defect in fibroblasts of the patient carrying the Asp446Asn mutation was rescued by transduction of wild type NDUFS2. A 3-D model of the catalytic core of complex I showed that the mutated amino acid residue resides near the coenzyme Q binding pocket. However, the K(M) of complex I for coenzyme Q analogs of the Asp446Asn mutated complex I was similar to the K(M) observed in other complex I defects and in controls. We propose that the mutation interferes with the reduction of coenzyme Q or with the coupling of coenzyme Q reduction with the conformational changes involved in proton pumping of complex I.

Topics: Amino Acid Sequence; Animals; Cardiomyopathy, Hypertrophic; Catalysis; Electron Transport Complex I; Female; Fibroblasts; Homozygote; Humans; Infant; Infant, Newborn; Leigh Disease; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Membranes; Models, Molecular; Molecular Sequence Data; Mutation; NADH Dehydrogenase; Protein Conformation; Transduction, Genetic; Ubiquinone

The CHDI Fifth Annual HD Therapeutics Conference, held in Palm Springs, CA, included topics covering new therapeutic developments in the field of Huntington's disease (HD). This conference report highlights presentations on biomarkers in HD; emerging topics in drug targeting, such as the lysosomal degradation pathway and target prediction by network-based modeling; understanding phenotype and neuronal circuit dysfunction in animal models; regulation of huntingtin protein expression and function; RNAi and antisense technology to deplete the mutant huntingtin protein; and small-molecule drugs that are progressing quickly through the clinic. Investigational drugs discussed include ALN-HTT (Alnylam Pharmaceuticals Inc/Medtronic Inc), EPI-743 (Edison Pharmaceuticals Inc), LNK-754 (Link Medicine Corp) and pridopidine (NeuroSearch A/S).

Topics: Animals; Biomarkers; Disease Models, Animal; Dopamine; Drug Delivery Systems; Enzyme Inhibitors; Farnesyltranstransferase; Humans; Huntingtin Protein; Huntington Disease; Leigh Disease; Lysosomes; Models, Biological; Nerve Tissue Proteins; Neurodegenerative Diseases; Nuclear Proteins; Oligonucleotides, Antisense; Phosphorylation; Piperidines; RNA, Small Interfering; Sheep; Sirtuin 1; Ubiquinone

Respiratory failure can be the direct cause of death in patients with Leigh syndrome. Unfortunately, no effective treatment strategy is available. Here, we report successful treatment of a patient with Leigh syndrome using idebenone, a derivative of coenzyme Q-10. The patient's brainstem function, especially respiratory function, improved after idebenone treatment. Idebenone may be worth trying in patients with Leigh syndrome.

Topics: Adolescent; Brain Stem; Evoked Potentials, Auditory, Brain Stem; Follow-Up Studies; Humans; Lactic Acid; Leigh Disease; Male; Polysomnography; Respiration; Respiratory Insufficiency; Ubiquinone

Mitochondrial myopathies are regulated by two genomes: the nuclear DNA, and the mitochondrial DNA. While, so far, most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial DNA, a new field of investigation is that of syndromes due to mutations in the nuclear DNA. These latter disorders have mendelian inheritance.. Three representative cases have been selected: one with COX deficiency and a Leigh syndrome due to a SURF1 gene mutation, one due to a defect of Coenzyme Q synthesis and one with dominant optic atrophy due to a mutation in the OPA1 gene.. Future developments will show that many neurodegenerative disorders are due to mutations of nuclear genes controlling mitochondrial function, fusion and fission.

Topics: Cell Nucleus; Child; DNA; Female; Genome; GTP Phosphohydrolases; Humans; Infant; Leigh Disease; Male; Membrane Proteins; Middle Aged; Mitochondrial Diseases; Mitochondrial Proteins; Mutation; Optic Atrophy; Prostaglandin-Endoperoxide Synthases; Ubiquinone

Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III. Deficiency of CoQ(10) has been associated with diverse clinical phenotypes, but, in most patients, the molecular cause is unknown. The first defect in a CoQ(10) biosynthetic gene, COQ2, was identified in a child with encephalomyopathy and nephrotic syndrome and in a younger sibling with only nephropathy. Here, we describe an infant with severe Leigh syndrome, nephrotic syndrome, and CoQ(10) deficiency in muscle and fibroblasts and compound heterozygous mutations in the PDSS2 gene, which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ(10) biosynthetic pathway. Biochemical assays with radiolabeled substrates indicated a severe defect in decaprenyl diphosphate synthase in the patient's fibroblasts. This is the first description of pathogenic mutations in PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ(10) deficiency.

Topics: Alkyl and Aryl Transferases; Biotin; Carnitine; Case-Control Studies; Cells, Cultured; Coenzymes; Fibroblasts; Humans; Infant; Kidney Diseases; Leigh Disease; Muscle Hypotonia; Mutation; Protein Subunits; Riboflavin; Thiamine; Ubiquinone

Predominant cerebellar involvement has not been previously reported as a common neuroradiologic feature in pediatric mitochondrial cytopathies. Here we report the neuroradiologic findings of predominant cerebellar volume loss in children with various mitochondrial disorders.. A retrospective analysis of the medical records of 400 consecutive patients referred for evaluation of mitochondrial encephalomyopathies was performed. In 113 cases, definite diagnosis of mitochondrial disease was based on the modified adult criteria that include clinical, histologic, biochemical, functional, molecular, and metabolic parameters.. Predominant cerebellar volume loss with progressive cerebellar atrophy and, less often, cerebellar hypoplasia were found in a heterogeneous group of patients with mitochondrial disease that consisted of four patients with complex I deficiency; four patients with multiple respiratory chain deficiencies; two patients with combined complex I + III and II + III deficiencies, including one patient with partial coenzyme Q10 deficiency; three patients with complex II deficiency; two patients with complex IV deficiency; one patient with mitochondrial neurogastrointestinal encephalomyopathy; and two patients with mitochondrial encephalomyopathy, lactic acidosis, and strokes.. Our retrospective study shows that isolated or predominant cerebellar involvement can be found in various respiratory chain defects or mitochondrial disorders expanding the classical neuroradiologic findings observed in mitochondrial encephalomyopathies. The diagnostic workup in patients with neuromuscular features whose brain MR imaging exhibits cerebellar volume loss should include the evaluation for mitochondrial encephalomyopathies.

Topics: Acidosis, Lactic; Adolescent; Adult; Cerebellum; Child; Child, Preschool; Female; Humans; Infant; Leigh Disease; Magnetic Resonance Imaging; Male; Metabolism, Inborn Errors; Mitochondrial Encephalomyopathies; Multienzyme Complexes; Retrospective Studies; Stroke; Ubiquinone

Leigh syndrome (LS) is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Typically, signs and symptoms commence in infancy or childhood, although rare cases of adult onset have been described. Progressive deterioration is the norm. The authors describe a 22-year-old woman with partial cytochrome c oxidase deficiency who developed fulminant LS following an acute febrile illness and who subsequently showed dramatic clinical and neuroradiologic improvement.

Topics: Adult; Ascorbic Acid; Brain; Cytochrome-c Oxidase Deficiency; Drug Therapy, Combination; Female; Humans; Leigh Disease; Magnetic Resonance Imaging; Remission Induction; Riboflavin; Thiamine; Ubiquinone

CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

Topics: Biopsy; Electron Transport Complex I; Electron Transport Complex II; Electron Transport Complex III; Hearing Loss, Sensorineural; Humans; Hyperammonemia; Infant; Leigh Disease; Liver; Liver Failure, Acute; Male; Metabolism, Inborn Errors; Mitochondria, Liver; Mitochondrial Diseases; Oxidative Phosphorylation; Pancreas; Ubiquinone

A 31-year-old woman had encephalopathy, growth retardation, infantilism, ataxia, deafness, lactic acidosis, and increased signals of caudate and putamen on brain magnetic resonance imaging. Muscle biochemistry showed succinate:cytochrome c oxidoreductase (complex II-III) deficiency. Both clinical and biochemical abnormalities improved remarkably with coenzyme Q10 supplementation. Clinically, when taking 300mg coenzyme Q10 per day, she resumed walking, gained weight, underwent puberty, and grew 20cm between 24 and 29 years of age. Coenzyme Q10 was markedly decreased in cerebrospinal fluid, muscle, lymphoblasts, and fibroblasts, suggesting the diagnosis of primary coenzyme Q10 deficiency. An older sister has similar clinical course and biochemical abnormalities. These findings suggest that coenzyme Q10 deficiency can present as adult Leigh's syndrome.

Topics: Adult; Coenzymes; Female; Humans; Leigh Disease; Magnetic Resonance Imaging; Siblings; Ubiquinone