Specifically, the enzyme is responsible for the third step in processing leucine, an essential amino acid. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, isovaleric acid and related compounds build up to toxic levels, damaging the brain and nervous system. Diagnosis
The urine of newborns can be screened for isovaleric acidemia using mass spectrometry, allowing for early diagnosis. Elevations of isovalerylglycine in urine and of isovalerylcarnitine in plasma are found. Screening
On 9 May 2014, the UK National Screening Committee (UK NSC) announced its recommendation to screen every newborn baby in the UK for four further genetic disorders as part of its NHS Newborn Blood Spot Screening programme, including isovaleric acidemia. Treatment
Treatment consists of dietary protein restriction, particularly leucine. During acute episodes, glycine is sometimes given, which conjugates with isovalerate forming isovalerylglycine, or carnitine which has a similar effect. Elevated 3-hydroxyisovaleric acid is a clinical biomarker of biotin deficiency. Without biotin, leucine and isoleucine cannot be metabolized normally and results in elevated synthesis of isovaleric acid and consequently 3-hydroxyisovaleric acid, isovalerylglycine, and other isovaleric acid metabolites as well. Elevated serum 3-hydroxyisovaleric acid concentrations can be caused by supplementation with 3-hydroxyisovaleric acid, genetic conditions, or dietary deficiency of biotin. Some patients with isovaleric acidemia may benefit from supplemental biotin. Biotin deficiency on its own can have severe physiological and cognitive consequences that closely resemble symptoms of organic acidemias.
Butalbital is a barbiturate with an intermediate duration of action. Butalbital is often combined with other medications, such as paracetamol (acetaminophen) or aspirin, for the treatment of pain and headache. The various formulations combined with codeine are FDA-approved for the treatment of tension headaches. Butalbital has the same chemical formula as talbutal but a different structure—one that presents as 5-allyl-5-isobutylbarbituric acid. Preparations
Combinations include:

Butalbital and acetaminophen (paracetamol) (trade names: Axocet, Bucet, Bupap, Cephadyn, Dolgic, Phrenilin, Forte, Sedapap)
Butalbital, paracetamol (acetaminophen), and caffeine (trade names: Fioricet, Esgic, Esgic-Plus, Orbivan, Fiorinal, Fiormor, Fiortal, Fortabs, Laniroif)
Butalbital, paracetamol (acetaminophen), caffeine, and codeine phosphate (trade name: Fioricet#3 with Codeine)
Butalbital and aspirin (trade name: Axotal)
Butalbital, aspirin, caffeine, and codeine phosphate (trade name: Fiorinal#3 with Codeine)
Ergotamine tartrate, caffeine, butalbital, belladonna alkaloids (trade name: Cafergot-PB)

Contraindications
There are specific treatments which are appropriate for targeting migraines and headaches. Butalbital is not recommended as a first-line treatment because it impairs alertness, brings risk of dependence and addiction, and increases the risk that episodic headaches will become chronic. When other treatments  are unavailable or ineffective, butalbital may be appropriate if the patient can be monitored to prevent the development of chronic headache. Side effects
Side effects for any psychoactive drug are difficult to predict, though butalbital is usually well tolerated. Commonly reported side effects for butalbital, some of which tend to subside with continued use, include:

Rare side-effects include Stevens–Johnson syndrome, an adverse reaction to barbiturates, and anaphylaxis. The risk and severity of all side effects is greatly increased when butalbital (or butalbital-containing medications) are combined with other sedatives (ex.