2-Methylbutyryl-CoA dehydrogenase deficiency is an

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosom ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter t ...

. It causes the body to be unable to process the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

isoleucine properly. Initial case reports identified individuals with

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech ...

and

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

, however most cases identified through

newborn screening Newborn screening (NBS) is a public health program of screening in infants shortly after birth for conditions that are treatable, but not clinically evident in the newborn period. The goal is to identify infants at risk for these conditions e ...

have been asymptomatic.

Signs and symptoms

SBCADD is included as a secondary target condition in most

programs, as the key analyte is the same as is used to identify

isovaleric acidemia Isovaleric acidemia is a rare autosomal recessive metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia. Symptoms and signs A characteristic featu ...

. Most cases have been

Hmong Hmong may refer to: * Hmong people, an ethnic group living mainly in Southwest China, Vietnam, Laos, and Thailand * Hmong cuisine * Hmong customs and culture ** Hmong music ** Hmong textile art * Hmong language, a continuum of closely related to ...

individuals, who are asymptomatic. There are isolated case reports where individuals have been identified with SBCADD in addition to

and

. It is currently unclear what the complete clinical presentation of SBCADD looks like. There is some concern that these cases with additional symptoms may reflect an

ascertainment bias In statistics, sampling bias is a bias in which a sample is collected in such a way that some members of the intended population have a lower or higher sampling probability than others. It results in a biased sample of a population (or non-human f ...

rather than being a true representation of the clinical spectrum of the disease. Currently, there is no accepted treatment, as most affected individuals do not require any. Some recommend avoidance of

valproic acid Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...

, as it can be a substrate for 2-methylbutyryl-CoA dehydrogenase.

Cause

The disorder is caused by a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...

in the '' ACADSB''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

, located on the long arm of human

chromosome 10 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

(10q25-q26). It is inherited in an autosomal recessive manner, which means an affected individual must inherit one copy of the mutation from each parent.

Diagnosis

Most individuals with SBCADD are identified through

, where they present with an elevation of a five carbon acylcarnitine species. Confirmatory testing includes plasma and

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

analysis to identify the carnitine and

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...

conjugates of 2-methylbutyryl-CoA.

Treatment

References

External links

{{Amino acid metabolic pathology Amino acid metabolism disorders Autosomal recessive disorders Hmong