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
ICD-10: E71.3
UMLs:
MeSH:
MedDRA:
Snomed:

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: Sort by abundance 

1
(HPO:0003128) Lactic acidosis 26826406 IBIS 116 / 7739
2
(HPO:0001943) Hypoglycemia 17564966 IBIS 131 / 7739
3
(HPO:0003215) Dicarboxylic aciduria Occasional [HPO:probinson] 17564966 IBIS 7 / 7739
4
(HPO:0001638) Cardiomyopathy 25721401 IBIS 192 / 7739
5
(HPO:0001639) Hypertrophic cardiomyopathy 26669660 IBIS 137 / 7739
6
(HPO:0001644) Dilated cardiomyopathy 17564966 IBIS 141 / 7739
7
(HPO:0001635) Congestive heart failure 17564966 IBIS 232 / 7739
8
(HPO:0008972) Decreased activity of mitochondrial respiratory chain 26669660 IBIS 34 / 7739
9
(HPO:0002181) Cerebral edema 17564966 IBIS 19 / 7739
10
(HPO:0001414) Microvesicular hepatic steatosis 17564966 IBIS 9 / 7739
11
(HPO:0001992) Organic aciduria 17564966 IBIS 28 / 7739
12
(HPO:0001252) Muscular hypotonia 23996478 IBIS 990 / 7739
13
(HPO:0008947) Infantile muscular hypotonia 23996478 IBIS 482 / 7739
14
(HPO:0003546) Exercise intolerance 26669660 IBIS 62 / 7739
15
(HPO:0001324) Muscle weakness 26669660 IBIS 859 / 7739
16
(HPO:0001298) Encephalopathy 25721401 IBIS 72 / 7739
17
(HPO:0100543) Cognitive impairment 26669660 IBIS 230 / 7739
18
(HPO:0001250) Seizures 26669660 IBIS 1245 / 7739
19
(HPO:0001399) Hepatic failure 17564966 IBIS 80 / 7739
20
(HPO:0002910) Elevated hepatic transaminases 17564966 IBIS 158 / 7739
21
(HPO:0000114) Proximal tubulopathy 26669660 IBIS 18 / 7739
22
(HPO:0000083) Renal insufficiency 26669660 IBIS 232 / 7739
23
(HPO:0001297) Stroke 17564966 IBIS 44 / 7739
24
(HPO:0001873) Thrombocytopenia 17564966 IBIS 224 / 7739
25
(HPO:0002919) Ketonuria 17564966 IBIS 18 / 7739
26
(HPO:0001522) Death in infancy 25721401 IBIS 275 / 7739
27
(MedDRA:10057597) Urine ketone body present 17564966 IBIS 1 / 7739
28
(OMIM) Cerebellar stroke 17564966 IBIS 1 / 7739
29
(OMIM) Decreased mitochondrial complex I activity 26669660 IBIS 2 / 7739
30
(OMIM) Elevated lactate dehydrogenase 17564966 IBIS 4 / 7739
31
(OMIM) Elevated liver transaminases 17564966 IBIS 2 / 7739
32
(OMIM) Elevated plasma ammonia 17564966 IBIS 1 / 7739
33
(OMIM) Elevated prothrombin time 17564966 IBIS 1 / 7739
34
(OMIM) Elevated serum lactate 17564966 IBIS 1 / 7739
35
(OMIM) Hypoketotic dicarboxylic aciduria (in some patients) 17564966 IBIS 1 / 7739
36
(OMIM) Increased urinary lactate 17564966 IBIS 4 / 7739
37
(OMIM) Liver necrosis 17564966 IBIS 2 / 7739
38
(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 RCV000201736.1
ACAD9 rs150283105 pathogenic RCV000201643.1
ACAD9 rs368949613 pathogenic RCV000023865.2
ACAD9 rs377022708 pathogenic RCV000201606.1
ACAD9 rs377022708 pathogenic RCV000023869.3
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 ...