Lifetime exercise intolerance with lactic acidosis as key manifestation of novel compound heterozygous ACAD9 mutations causing complex I deficiency
| Autor: | Sarunas Augustis, Peter Schneiderat, Rita Horvath, Angela Abicht, Thomas Klopstock, Bertold Schrank, Elke Holinski-Feder, Benedikt Schoser |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Candidate gene Mitochondrial Diseases genetics [Mitochondrial Diseases] Compound heterozygosity pathology [Acidosis Lactic] pathology [Muscle Skeletal] 0302 clinical medicine Acyl-CoA Dehydrogenases Mitochondrial respiratory chain complex I physiology [Exercise Tolerance] Genetics (clinical) physiopathology [Acidosis Lactic] Exercise Tolerance medicine.diagnostic_test drug therapy [Acidosis Lactic] Phenotype Neurology genetics [Acidosis Lactic] Lactic acidosis Vomiting Acidosis Lactic Female medicine.symptom Adult medicine.medical_specialty Heterozygote Nausea drug therapy [Mitochondrial Diseases] genetics [Acyl-CoA Dehydrogenases] Exercise intolerance Diagnosis Differential 03 medical and health sciences Internal medicine medicine physiopathology [Mitochondrial Diseases] Humans ddc:610 Muscle Skeletal Muscle biopsy Electron Transport Complex I business.industry ACAD9 protein human medicine.disease deficiency [Electron Transport Complex I] pathology [Mitochondrial Diseases] 030104 developmental biology Endocrinology genetics [Exercise Tolerance] Pediatrics Perinatology and Child Health Mutation Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscular disorders 27(5), 473-476 (2017). doi:10.1016/j.nmd.2017.02.005 |
| ISSN: | 1873-2364 |
| DOI: | 10.1016/j.nmd.2017.02.005 |
| Popis: | We report a 36-year-old female having lifetime exercise intolerance and lactic acidosis with nausea associated with novel compound heterozygous Acyl-CoA dehydrogenase 9 gene (ACAD9) mutations (p.Ala390Thr and p.Arg518Cys). ACAD9 is an assembly factor for the mitochondrial respiratory chain complex I. ACAD9 mutations are recognized as frequent causes of complex I deficiency. Our patient presented with exercise intolerance, rapid fatigue, and nausea since early childhood. Mild physical workload provoked the occurrence of nausea and vomiting repeatedly. Her neurological examination, laboratory findings and muscle biopsy demonstrated no abnormalities. A bicycle spiroergometry provoked significant lactic acidosis during and following exercise pointing towards a mitochondrial disorder. Subsequently, the analysis of respiratory chain enzyme activities in muscle revealed severe isolated complex I deficiency. Candidate gene sequencing revealed two novel heterozygous ACAD9 mutations. This patient report expands the mutational and phenotypic spectrum of diseases associated with mutations in ACAD9. |
| Databáze: | OpenAIRE |
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