Acyl-CoA dehydrogenase 9 deficiency
General Information (adopted from Orphanet):
Synonyms, Signs: |
ACAD9 deficiency Mitochondrial complex I deficiency due to ACAD9 deficiency |
Number of Symptoms | 38 |
OrphanetNr: | 99901 |
OMIM Id: |
611126
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ICD-10: |
E71.3 |
UMLs: |
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MeSH: |
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MedDRA: |
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Snomed: |
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Prevalence, inheritance and age of onset:
Prevalence: | No data available. |
Inheritance: |
Autosomal recessive Monogenic PMID:22499348 [IBIS] |
Age of onset: |
Neonatal Infancy Childhood PMID:26669660 [IBIS] |
Disease classification (adopted from Orphanet):
Parent Diseases: |
Exercise intolerance with lactic acidosis
-Rare developmental defect during embryogenesis -Rare genetic disease -Rare neurologic disease Fatty acid oxidation and ketogenesis disorder with dilated cardiomyopathy -Rare cardiac disease -Rare genetic disease Fatty acid oxidation and ketogenesis disorder with hypertrophic cardiomyopathy -Rare cardiac disease -Rare genetic disease |
Comment:
Acyl-CoA dehydrogenase 9 (ACAD9) is an assembly factor for mitochondrial respiratory chain Complex I (CI). The tissue specificity of ACAD9 expression is high in liver and neurons and minimal in skin fibroblasts. Mutations in ACAD9 lead to CI deficiency independent of their effects on ACAD enzyme activity. Patients with CI deficiency caused by ACAD9 mutations display a broad range of clinical severity (PMID:25721401). Age of onset ranged from neonatal period to 9 years and 5/8 died in infancy and 5/8 died in infancy (PMID:26669660). |
Symptom Information:
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(HPO:0003128) | Lactic acidosis | 26826406 | IBIS | 116 / 7739 | ||
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(HPO:0001943) | Hypoglycemia | 17564966 | IBIS | 131 / 7739 | ||
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(HPO:0003215) | Dicarboxylic aciduria | Occasional [HPO:probinson] | 17564966 | IBIS | 7 / 7739 | |
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(HPO:0001638) | Cardiomyopathy | 25721401 | IBIS | 192 / 7739 | ||
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(HPO:0001639) | Hypertrophic cardiomyopathy | 26669660 | IBIS | 137 / 7739 | ||
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(HPO:0001644) | Dilated cardiomyopathy | 17564966 | IBIS | 141 / 7739 | ||
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(HPO:0001635) | Congestive heart failure | 17564966 | IBIS | 232 / 7739 | ||
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(HPO:0008972) | Decreased activity of mitochondrial respiratory chain | 26669660 | IBIS | 34 / 7739 | ||
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(HPO:0002181) | Cerebral edema | 17564966 | IBIS | 19 / 7739 | ||
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(HPO:0001414) | Microvesicular hepatic steatosis | 17564966 | IBIS | 9 / 7739 | ||
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(HPO:0001992) | Organic aciduria | 17564966 | IBIS | 28 / 7739 | ||
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(HPO:0001252) | Muscular hypotonia | 23996478 | IBIS | 990 / 7739 | ||
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(HPO:0008947) | Infantile muscular hypotonia | 23996478 | IBIS | 482 / 7739 | ||
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(HPO:0003546) | Exercise intolerance | 26669660 | IBIS | 62 / 7739 | ||
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(HPO:0001324) | Muscle weakness | 26669660 | IBIS | 859 / 7739 | ||
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(HPO:0001298) | Encephalopathy | 25721401 | IBIS | 72 / 7739 | ||
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(HPO:0100543) | Cognitive impairment | 26669660 | IBIS | 230 / 7739 | ||
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(HPO:0001250) | Seizures | 26669660 | IBIS | 1245 / 7739 | ||
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(HPO:0001399) | Hepatic failure | 17564966 | IBIS | 80 / 7739 | ||
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(HPO:0002910) | Elevated hepatic transaminases | 17564966 | IBIS | 158 / 7739 | ||
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(HPO:0000114) | Proximal tubulopathy | 26669660 | IBIS | 18 / 7739 | ||
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(HPO:0000083) | Renal insufficiency | 26669660 | IBIS | 232 / 7739 | ||
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(HPO:0001297) | Stroke | 17564966 | IBIS | 44 / 7739 | ||
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(HPO:0001873) | Thrombocytopenia | 17564966 | IBIS | 224 / 7739 | ||
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(HPO:0002919) | Ketonuria | 17564966 | IBIS | 18 / 7739 | ||
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(HPO:0001522) | Death in infancy | 25721401 | IBIS | 275 / 7739 | ||
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(MedDRA:10057597) | Urine ketone body present | 17564966 | IBIS | 1 / 7739 | ||
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(OMIM) | Cerebellar stroke | 17564966 | IBIS | 1 / 7739 | ||
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(OMIM) | Decreased mitochondrial complex I activity | 26669660 | IBIS | 2 / 7739 | ||
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(OMIM) | Elevated lactate dehydrogenase | 17564966 | IBIS | 4 / 7739 | ||
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(OMIM) | Elevated liver transaminases | 17564966 | IBIS | 2 / 7739 | ||
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(OMIM) | Elevated plasma ammonia | 17564966 | IBIS | 1 / 7739 | ||
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(OMIM) | Elevated prothrombin time | 17564966 | IBIS | 1 / 7739 | ||
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(OMIM) | Elevated serum lactate | 17564966 | IBIS | 1 / 7739 | ||
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(OMIM) | Hypoketotic dicarboxylic aciduria (in some patients) | 17564966 | IBIS | 1 / 7739 | ||
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(OMIM) | Increased urinary lactate | 17564966 | IBIS | 4 / 7739 | ||
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(OMIM) | Liver necrosis | 17564966 | IBIS | 2 / 7739 | ||
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(OMIM) | Reye-like episode | 17564966 | IBIS | 1 / 7739 |
Associated genes:
ACAD9; |
ClinVar (via SNiPA)
Gene symbol | Variation | Clinical significance | Reference |
---|---|---|---|
ACAD9 | rs115532916 | pathogenic | RCV000023868.2 |
ACAD9 | rs150283105 | pathogenic | RCV000201643.1 |
ACAD9 | rs150283105 | pathogenic | RCV000201736.1 |
ACAD9 | rs368949613 | pathogenic | RCV000023865.2 |
ACAD9 | rs377022708 | pathogenic | RCV000023869.3 |
ACAD9 | rs377022708 | pathogenic | RCV000201606.1 |
ACAD9 | rs387906242 | pathogenic | RCV000001073.3 |
ACAD9 | rs387907041 | pathogenic | RCV000023866.2 |
ACAD9 | rs387907042 | pathogenic | RCV000023867.3 |
ACAD9 | rs753711253 | pathogenic | RCV000201531.1 |
ACAD9 | rs770127110 | pathogenic | RCV000201693.1 |
ACAD9 | rs773586510 | pathogenic | RCV000201722.1 |
ACAD9 | rs781156571 | pathogenic | RCV000201557.1 |
Additional Information:
Description: (OMIM) |
ACAD9 deficiency is an autosomal recessive multisystemic disorder characterized by infantile onset of acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness associated with a deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts (summary by Haack ... |
Clinical Description OMIM |
Haack et al. (2010) reported 4 patients, including 2 sibs, with mitochondrial complex I deficiency. In the 2 sibs, the sister presented soon after birth with cardiorespiratory depression, hypertrophic cardiomyopathy, encephalopathy, and severe lactic acidosis, and died at ... |
Molecular genetics OMIM |
In 4 patients, including 2 sibs, with mitochondrial complex I deficiency due to ACAD9 deficiency, Haack et al. (2010) identified compound heterozygosity for 2 mutations in the ACAD9 gene (611103.0002-611103.0006, respectively). The authors demonstrated the efficacy of exome ... |