Isovaleric acidemia

Classification according to ICD-10
E71.1	Other disorders of the metabolism of branched amino acids
ICD-10 online (WHO version 2019)

In the Isovalerianzidämie (IVA), also known as Isovaleranazidurie is referred to, is a congenital metabolic disorder from the group of Organazidopathien . The condition is inherited as an autosomal recessive trait. The breakdown pathway of the branched-chain amino acid leucine is affected .

The frequency of the disease ( prevalence ) is estimated at 1: 100,000 in Europe.

Pathogenesis

The breakdown of leucine takes place in several intermediate steps. This also creates isovaleric acid, which is further broken down in healthy metabolic conditions. Due to a defect in the enzyme isovaleryl-CoA dehydrogenase, isovaleric acid cannot be broken down and accumulates in the tissue. This leads to acidosis and a secondary impairment of other metabolic pathways.

Symptoms

In around half of those affected, the symptoms appear in the neonatal period. The infants can be noticed with poor drinking, vomiting, apathy and seizures.

In milder forms, symptoms only appear in older infants. Triggers such as gastroenteritis, respiratory tract infections or high protein intake can lead to critical deterioration.

diagnosis

In severe forms, hyperammonaemia , increased lactate levels and ketoacidosis occur . The diagnosis can be recognized in the context of a newborn screening by means of tandem mass spectrometry.

A molecular genetic examination is carried out to prove the genetic defect, so that the identification of mild forms is also possible.

therapy

Emergency treatment consists of stopping protein intake and correcting acidosis and hyperammonaemia .

In long-term therapy, there is a controlled reduction in the leucine intake (special food with a mixture of amino acids). Glycine and L-carnitine can be administered for binding and detoxification .

literature

Frank Jochum: Nutritional Medicine Pediatrics . Springer, Berlin / Heidelberg 2013, ISBN 978-3-642-29816-5 .

Web links

Isovaleric Acidemia. Omin
Isovaleric acidemia. Orphanet

Individual evidence

↑ E. Mönch: Infusion therapy and nutrition for congenital metabolic disorders . In: Nutritional Medicine, Pediatrics . Springer, Berlin / Heidelberg 2012, ISBN 978-3-642-29816-5 , p. 215-248 , doi : 10.1007 / 978-3-642-29817-2_21 .
↑ Sarah C Grünert, Udo Wendel, Martin Lindner, Michael Leichsenring, K Otfried Schwab: Clinical and neurocognitive outcome in symptomatic isovaleric acidemia . In: Orphanet Journal of Rare Diseases . tape 7 , no. 1 , 2012, ISSN 1750-1172 , p. 9 , doi : 10.1186 / 1750-1172-7-9 , PMID 22277694 , PMC 3292949 (free full text) - ( biomedcentral.com [accessed July 26, 2018]).
↑ K Tanaka, MA Budd, ML Efron, KJ Isselbacher: Isovaleric acidemia: a new genetic defect of leucine metabolism. In: Proceedings of the National Academy of Sciences . tape 56 , no. 1 , 1966, ISSN 0027-8424 , pp. 236-242 , PMID 5229850 , PMC 285701 (free full text).
Jump up ↑ Regina Ensenauer, Jerry Vockley, Jan-Marie Willard, Joseph C. Huey, Jörn Oliver Sass: A Common Mutation Is Associated with a Mild, Potentially Asymptomatic Phenotype in Patients with Isovaleric Acidemia Diagnosed by Newborn Screening . In: The American Journal of Human Genetics . tape 75 , no. 6 , December 2004, ISSN 0002-9297 , p. 1136–1142 , doi : 10.1086 / 426318 , PMID 15486829 , PMC 1182150 (free full text) - ( elsevier.com [accessed July 26, 2018]).

[1] E. Mönch: Infusion therapy and nutrition for congenital metabolic disorders . In: Nutritional Medicine, Pediatrics . Springer, Berlin / Heidelberg 2012, ISBN 978-3-642-29816-5 , p. 215-248 , doi : 10.1007 / 978-3-642-29817-2_21 .

[2] Sarah C Grünert, Udo Wendel, Martin Lindner, Michael Leichsenring, K Otfried Schwab: Clinical and neurocognitive outcome in symptomatic isovaleric acidemia . In: Orphanet Journal of Rare Diseases . tape 7 , no. 1 , 2012, ISSN 1750-1172 , p. 9 , doi : 10.1186 / 1750-1172-7-9 , PMID 22277694 , PMC 3292949 (free full text) - ( biomedcentral.com [accessed July 26, 2018]).

[3] K Tanaka, MA Budd, ML Efron, KJ Isselbacher: Isovaleric acidemia: a new genetic defect of leucine metabolism. In: Proceedings of the National Academy of Sciences . tape 56 , no. 1 , 1966, ISSN 0027-8424 , pp. 236-242 , PMID 5229850 , PMC 285701 (free full text).

[4] Jump up ↑ Regina Ensenauer, Jerry Vockley, Jan-Marie Willard, Joseph C. Huey, Jörn Oliver Sass: A Common Mutation Is Associated with a Mild, Potentially Asymptomatic Phenotype in Patients with Isovaleric Acidemia Diagnosed by Newborn Screening . In: The American Journal of Human Genetics . tape 75 , no. 6 , December 2004, ISSN 0002-9297 , p. 1136–1142 , doi : 10.1086 / 426318 , PMID 15486829 , PMC 1182150 (free full text) - ( elsevier.com [accessed July 26, 2018]).