Rare Diseases Science
IsobutyrylCoenzyme A dehydrogenase deficiency (isobutyryl-CoA dehydrogenase deficiency, IBDD, OMIM 611283) is an autosomal recessive genetic disease, which is caused by valine due to the impairment of isobutyryl-CoA dehydrogenase activity in the process of valine degradation. Metabolic disease. Because isobutyryl-CoA dehydrogenase deficiency is rare, only 22 cases have been reported worldwide, and there is no epidemiological data.
History
1998First reported by Roe et al. this disease. 1999Telford et al. successfully found the disease-causing gene ACAD8 and cloned it. 2007Oglesbee et al. reported 19 ACAD8 mutations.
Pathogenesis
isobutyryl coenzyme A dehydrogenase deficiency is caused by the decrease or lack of the activity of isobutyryl-CoA dehydrogenase encoded by the ACAD8 gene. This enzyme catalyzes the third step of the valine degradation reaction, resulting in the disorder of isobutyryl-CoA dehydrogenase activity. Isobutyryl-CoA cannot be degraded, and the metabolism of valine is hindered, which affects the energy supply of the body, and at the same time, the concentration of C4 (butyrylcarnitine) in the blood increases.
isobutyryl-CoA dehydrogenase deficiency caused by mutations in the ACAD8 gene. The gene ACAD8 is located at 11q25 and belongs to the acyl-CoA dehydrogenase gene family. ACAD8 is expressed in heart, lung, brain, skeletal muscle, pancreas, liver and kidney.
Clinical manifestations
Homozygous mutation was found by gene sequencing, but no obvious symptoms. Onset types:anemia,Retardation, dilated cardiomyopathy, muscle weakness.
Lab examination
Prenatal diagnosis: Chromosomal and genetic mutation analysis of high-risk parents. blood tandem mass spectrometry detection: C4 (butyrylcarnitine) concentration, C4/C2, valine concentration. Urine test:Isobutyrylglycine. Gene diagnosis: ACAD8 gene sequencing was performed on the patients.
principle of treatment Dietary therapy:Restricting valine intake in food can moderately reduce serum valine concentrations. L-Carnitine:Maintains the normal carnitine levels required by the body.
I am Dr. Yang and I am not responsible for medicine
Professor and Doctoral Supervisor of Pediatrics, Peking University First HospitalConcurrently:Beijing Head of the Genetics and Metabolism Group of the Rare Diseases Branch of the Medical Association, and Deputy Head of the Endocrine Genetics and Metabolism Group of the Pediatrics Branch; >Deputy head of the clinical nutrition group of the Pediatrics Branch of the Chinese Medical Association, consultant of the endocrine genetics and metabolism group;Member of the Standing Committee of the Birth Defect Prevention and Control Special Committee of the Chinese Preventive Medicine Association, newborn screening specialist Deputy head of the group; Deputy chairman of the China Birth Defects Intervention and Relief Foundation Children’s Genetic Metabolic Disease Expert Committee; Member of the Clinical Genetics Group of the Chinese Medical Doctor Association; Deputy Head of Biochemistry Group; Deputy Head of Neuroprosthetics Group of Pediatric Branch of Chinese Medical Doctor Association; Deputy Director of Expert Committee of Mitochondrial Disease Laboratory Medicine of Chinese Medical Doctor Association Laboratory Physician Branch. Director of Asian Society of Genetic Metabolic Diseases. Research direction:Diagnosis and treatment of genetic metabolic and endocrine diseases
Source: Yang Yanling Metabolism Collaborative Team
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