WordNet

a blood disorder characterized by an increased concentration of hydrogen ions in the blood (which falls below 7 on the pH scale)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/20 22:05:12」(JST)

wiki en

Isovaleric acidemia, also called isovaleric aciduria or isovaleric acid CoA dehydrogenase deficiency,^[1] is a rare autosomal recessive^[2] metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.^[3]

Symptoms

A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet.^[4] This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.

In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection or by eating an increased amount of protein-rich foods.

Diagnosis

The urine of newborns can be screened for isovaleric acidemia using mass spectrometry,^[3] allowing for early diagnosis. Elevations of isovalerylglycine in urine and of isovalerylcarnitine in plasma are found.

Genetics

Isovaleric acidemia has an autosomal recessive pattern of inheritance.

The disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Mutations in both copies of the IVD gene result in isovaleric acidemia.

Pathophysiology

The enzyme encoded by IVD, isovaleric acid-CoA dehydrogenase (EC 1.3.99.10), plays an essential role in breaking down proteins from the diet. 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.

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 hydroxyisovalerate is a clinical marker of biotin deficiency. Without biotin, leucine and isoleucine cannot be fully metabolized. This leads to the formation of hydroxyisovalerate instead of the normal useful byproducts of leucine and isoleucine catabolism. Elevated hydroxyisovalerate can be caused by genetic conditions or dietary deficiency of biotin, and many patients with organic acidemias related to incomplete leucine catabolism can benefit from supplemental biotin.^[5] Biotin deficiency on its own can have severe physiological and cognitive consequences ^[6] that closely resemble symptoms of organic acidemias.

Epidemiology

Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States.^[7]

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.^[8]

References

^ Online 'Mendelian Inheritance in Man' (OMIM) 243500
^ Lee, Yw; Lee, Dh; Vockley, J; Kim, Nd; Lee, Yk; Ki, Cs (September 2007). "Different spectrum of mutations of isovaleryl-CoA dehydrogenase (IVD) gene in Korean patients with isovaleric acidemia". Molecular genetics and metabolism 92 (1–2): 71–7. doi:10.1016/j.ymgme.2007.05.003. PMC 4136440. PMID 17576084.
^ ^a ^b Dionisi-Vici, C; Deodato, F; Röschinger, W; Rhead, W et al. (2006). "Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry". J Inherit Metab Dis. 29 (2–3): 383–389. doi:10.1007/s10545-006-0278-z. PMID 16763906.
^ Tokatli A, Oskun T, Ozalp I; Coşkun; Ozalp (1998). "Isovaleric acidemia. Clinical presentation of 6 cases". The Turkish Journal of Pediatrics 40 (1): 111–119. PMID 9673537.
^ http://www.ommbid.com/OMMBID/the_online_metabolic_and_molecular_bases_of_inherited_disease/b/abstract/part9/ch93
^ "Genova Diagnostics (GDX) - Diagnostic Laboratory Testing for Wellness & Preventive Medicine". metametrix.com.
^ "Isovaleric acidemia". Genetics Home Reference. 4 May 2015.
^ "New screening will protect babies from death and disability". screening.nhs.uk.

External links

Organic Acidemia Association
Isovaleric acidemia at NLM Genetics Home Reference
-187695062 at GPnotebook
GeneReviews: The Organic Acidemias

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 有機酸血症 organic acidemias
2. アレキサンダー病 alexander disease
3. 先天性代謝異常：疫学、病因、および臨床的特徴 inborn errors of metabolism epidemiology pathogenesis and clinical features
4. 幼児および小児における低血糖症の病因 etiology of hypoglycemia in infants and children
5. 小児および若年成人における虚血性脳卒中：病因と臨床的特徴 ischemic stroke in children and young adults etiology and clinical features

English Journal

Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study.

Hassan FA1, El-Mougy F1, Sharaf SA1, Mandour I1, Morgan MF1, Selim LA2, Hassan SA2, Salem F2, Oraby A2, Girgis MY2, Mahmoud IG3, El-Badawy A3, El-Nekhely I4, Moharam N4, Mehaney DA1, Elmonem MA5.
Journal of medical screening.J Med Screen.2016 Jan 20. pii: 0969141315618229. [Epub ahead of print]
OBJECTIVES: To estimate the burden of metabolic disorders detectable by tandem mass spectrometry in Egypt, through a pilot expanded newborn screening programme at Cairo University Children's Hospital in 2008, and examining the results of 3,900 clinically at-risk children, investigated at Cairo Unive
PMID 26790708

A Study on the Humoral and Complement Immune System of Patients with Organic Acidemia.

Alizadeh Najjarbashi F1, Mesdaghi M2, Alaei M3, Shakiba M3, Jami A4, Ghadimi F5.
Iranian journal of allergy, asthma, and immunology.Iran J Allergy Asthma Immunol.2015 Nov;14(6):638-41.
Patients with organic acidemia are prone to different infections, which lead to acidosis episodes. Some studies have evaluated the status of immune system in acidotic phase in these patients, but to the best of our knowledge no study has evaluated the immune system in non-acidotic phase of the disea
PMID 26725562

Elevation of pivaloylcarnitine by sivelestat sodium in two children.

Yamada K1, Kobayashi H2, Bo R3, Takahashi T2, Hasegawa Y2, Nakamura M4, Ishige N5, Yamaguchi S2.
Molecular genetics and metabolism.Mol Genet Metab.2015 Nov;116(3):192-4. doi: 10.1016/j.ymgme.2015.09.009. Epub 2015 Sep 26.
BACKGROUND: Sivelestat sodium (sivelestat), a neutrophil elastase inhibitor, is used to treat acute respiratory distress syndrome (ARDS). We report two cases that developed elevated C5-acylcarnitine (C5-AC) levels following treatment with sivelestat. Case 1 was a 14-day-old female infant born at 25
PMID 26428892

Japanese Journal

Stable-isotope dilution measurement of isovalerylglycine by tandem mass spectrometry in newborn screening for isovaleric acidemia

SHIGEMATSU Yosuke,HATA Ikue,TANAKA Yukie
Clinica chimica acta : international journal of clinical chemistry 386(1-2), 82-86, 2007-11
… BACKGROUND: Recent neonatal screening for isovaleric acidemia by tandem mass spectrometry based on dried blood-spot levels of C5-acylcarnitines, including isovalerylcarnitine and its isomer, pivaloylcarnitine, which is derived from pivalate-generating antibiotics, has caused many false-positive results. …
NAID 120001008436

Stable-isotope dilution measurement of isovalerylglycine by tandem mass spectrometry in newborn screening for isovaleric acidemia

Shigematsu Yosuke,Ikue Hata,Tanaka Yukie
Clinica Chimica Acta 386(1-2), 82-86, 2007-11
… Background: Recent neonatal screening for isovaleric acidemia by tandem mass spectrometry based on dried blood spot levels of C5-acylcarnitines, including isovalerylcarnitine and its isomer, pivaloylcarnitine, which is derived from pivalate-generating antibiotics, has caused many false-positive results. …
NAID 120000807738