3-Hydroxyisobutyryl-CoA deacylase deficiency is a rare autosomal recessive condition that is associated with severely delayed psychomotor development, neurodegeneration, increased lactic acid and brain lesions in the basal ganglia.[1] Fewer than 10 patients have been described with this condition.
| 3-Hydroxyisobutyryl-CoA deacylase deficiency | |
|---|---|
 | |
| Autosomal recessive pattern is the inheritance manner of this condition | |
| Specialty | Medical genetics |
Signs and symptoms edit
These include:[citation needed]
- Delayed motor development
- Hypotonia
- Progressive neurodegeneration
- Seizures
Genetics edit
This condition is caused by mutations in the HIBCH gene. This gene is located on the long arm of chromosome 2 (2q32).[citation needed]
Pathogenesis edit
This enzyme is involved in the metabolism of the amino acid valine. Mutations in this enzyme result in the accumulation of methacrylic acid. When this acid is acetylated, it is very reactive with free sulfhydryl groups. When the levels of this enzymes are too low valine levels increase, particularly in the mitochondria.[citation needed]
How this produces the clinical picture is not yet clear.
Diagnosis edit
This is difficult on clinical grounds alone. It may be suspected by examination of the urine for conjugates of methacrylic acid. The diagnosis is made by sequencing the mutated gene.[citation needed]
Differential diagnosis edit
Treatment edit
There is currently no curative treatment for this condition. Supportive management is all that is currently available.[citation needed]
History edit
This condition was first described in 1982.[2]
References edit
- ^ Yamada, Kenichiro; Naiki, Misako; Hoshino, Shin; Kitaura, Yasuyuki; Kondo, Yusuke; Nomura, Noriko; Kimura, Reiko; Fukushi, Daisuke; Yamada, Yasukazu; Shimozawa, Nobuyuki; Yamaguchi, Seiji; Shimomura, Yoshiharu; Miura, Kiyokuni; Wakamatsu, Nobuaki (2014). "Clinical and biochemical characterization of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency that causes Leigh-like disease and ketoacidosis". Molecular Genetics and Metabolism Reports. 1: 455–460. doi:10.1016/j.ymgmr.2014.10.003. PMC 5121361. PMID 27896122.
- ^ Brown, GK; Hunt, SM; Scholem, R; Fowler, K; Grimes, A; Mercer, JF; Truscott, RM; Cotton, RG; Rogers, JG; Danks, DM (October 1982). "Beta-hydroxyisobutyryl coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations". Pediatrics. 70 (4): 532–8. doi:10.1542/peds.70.4.532. PMID 7122152.