Isobutyryl-CoA dehydrogenase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: Acyl-CoA dehydrogenase family, member 8, deficiency of
ACAD8 deficiency
Isobutyric aciduria
IBD deficiency
Number of Symptoms 14
OrphanetNr: 79159
OMIM Id: 611283
ICD-10: E71.1
UMLs: C1969809
MeSH: C535541
MedDRA:
Snomed: 445274004

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
17304052 [IBIS]
Age of onset: Infancy
9889013 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Classic organic aciduria
 -Rare genetic disease
Syndrome associated with dilated cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease

Comment:

The hallmark of this defect in valine metabolism is an elevated intramitochondrial accumulation of isobutyryl-CoA that is shuttled outside the cell after esterification to isobutyrylcarnitine. The latter is detectable in plasma, urine, and blood spot samples as a C4-acylcarnitine that also represents an isomer, butyrylcarnitine, when analyzed using standard MS/MS-based procedures for acylcarnitine analysis. To date, 10 of the 13 isobutyryl-CoA dehydrogenase-deficient patients remain asymptomatic, two were lost to follow-up, and one patient required frequent hospitalizations due to emesis and dehydration but is developing normally at 5 years of age. Based on the newborn screening experience, the incidence of this autosomal recessive condition is at least 1:70,000 livebirths (PMID:17304052).

Symptom Information: Sort by abundance 

1
 (HPO:0002013) Vomiting 17304052; 12736383 IBIS 191 / 7739
2
 (HPO:0002099) Asthma 12736383 IBIS 62 / 7739
3
 (HPO:0001640) Cardiomegaly 9889013 IBIS 81 / 7739
4
 (HPO:0001631) Atria septal defect 9889013 IBIS 274 / 7739
5
 (HPO:0001644) Dilated cardiomyopathy 9889013 IBIS 141 / 7739
6
 (HPO:0004969) Peripheral pulmonary artery stenosis 17304052; 16857760 IBIS 9 / 7739
7
 (HPO:0003234) Decreased plasma carnitine 9889013 IBIS 9 / 7739
8
 (HPO:0001903) Anemia 9889013 IBIS 289 / 7739
9
 (HPO:0001944) Dehydration 17304052 IBIS 59 / 7739
10
 (HPO:0012330) Pyelonephritis 12736383 IBIS 7 / 7739
11
 (HPO:0001252) Muscular hypotonia 17304052; 15505379 IBIS 990 / 7739
12
 (HPO:0011342) Mild global developmental delay 17304052; 15505379 IBIS 10 / 7739
13
 (HPO:0000750) Delayed speech and language development 17304052; 16857760 IBIS 197 / 7739
14
 (HPO:0003265) Neonatal hyperbilirubinemia 12736383 IBIS 6 / 7739

Associated genes:

ACAD8;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
ACAD8 rs121908418 pathogenic RCV000005686.2
ACAD8 rs121908419 pathogenic RCV000005687.2
ACAD8 rs121908420 pathogenic RCV000005688.2
ACAD8 rs121908421 pathogenic RCV000005689.2
ACAD8 rs121908422 pathogenic RCV000005690.2

Additional Information:

Diagnosis OMIM Oglesbee et al. (2007) described an algorithm for the diagnosis of IBD deficiency identified by elevated C4-acylcarnitine on newborn screening. They noted that urine acylcarnitine analysis appeared to be a practical tool for diagnosing IBD deficiency.
Clinical Description OMIM The first patient with isobutyryl-CoA dehydrogenase (IBD) deficiency was described by Roe et al. (1998) and presented at age 12 months with dilated cardiomyopathy, anemia, and carnitine deficiency. An elevated C4-acylcarnitine was noted in a plasma acylcarnitine profile, ...
Molecular genetics OMIM Nguyen et al. (2002) found mutation in the ACAD8 gene in the patient described by Roe et al. (1998) (604773.0005).

Oglesbee et al. (2007) found 10 different mutations in the ACAD8 gene in 9 individuals with ...