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Normal Function
The AASS gene provides instructions for making an enzyme called alpha-aminoadipic semialdehyde synthase. This enzyme is found in many tissues, including the liver.
Alpha-aminoadipic semialdehyde synthase is involved in the breakdown of lysine, which is a building block (amino acid) of many different proteins. Amino acids are broken down when they are no longer needed. Alpha-aminoadipic semialdehyde synthase is called a bifunctional enzyme because it performs two functions during the breakdown of lysine. First, it converts lysine to a molecule called saccharopine, and then it converts saccharopine to a molecule called alpha-aminoadipic semialdehyde.
Health Conditions Related to Genetic Changes
Hyperlysinemia
Several variants (also called mutations) in the AASS gene have been found to cause hyperlysinemia, an inherited condition that is characterized by elevated levels of lysine in the blood. The signs and symptoms that have been reported in people with hyperlysinemia have varied widely, even among members of the same family. In addition, as many as 50 percent of people with this condition may be asymptomatic, which means that they do not have any signs or symptoms of the disorder.
The gene variants that cause hyperlysinemia reduce the activity of alpha-aminoadipic semialdehyde synthase. This can lead to a buildup of lysine in the blood. Variants in the AASS gene can cause one of two types of hyperlysinemia, depending on which steps of lysine breakdown are interrupted. In people with type I, the breakdown of lysine and saccharopine are both disrupted. In people with type II, it is mainly the breakdown of saccharopine that is impaired.
Researchers do not understand why some people with hyperlysinemia have signs and symptoms, while others do not. It is also unclear how higher levels of lysine in the blood cause the specific signs and symptoms seen in some people with hyperlysinemia. More research is needed to fully understand the effects of hyperlysinemia on the body.
More About This Health ConditionOther Names for This Gene
- alpha-aminoadipate semialdehyde synthase
- LKR/SDH
- LKRSDH
- LORSDH
- lysine-ketoglutarate reductase /saccharopine dehydrogenase
- saccharopine dehydrogenase (NAD(+), L-glutamate-forming)
- saccharopine dehydrogenase (NADP(+), L-lysine-forming)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Houten SM, Te Brinke H, Denis S, Ruiter JP, Knegt AC, de Klerk JB, Augoustides-Savvopoulou P, Haberle J, Baumgartner MR, Coskun T, Zschocke J, Sass JO, Poll-The BT, Wanders RJ, Duran M. Genetic basis of hyperlysinemia. Orphanet J Rare Dis. 2013 Apr 9;8:57. doi: 10.1186/1750-1172-8-57. Citation on PubMed
- Marinella G, Pascarella F, Vetro A, Bonuccelli A, Pochiero F, Santangelo A, Alessandri MG, Pasquariello R, Orsini A, Battini R. Hyperlysinemia, an ultrarare inborn error of metabolism: Review and update. Seizure. 2024 Aug;120:135-141. doi: 10.1016/j.seizure.2024.06.020. Epub 2024 Jun 24. Citation on PubMed
- Markovitz PJ, Chuang DT, Cox RP. Familial hyperlysinemias. Purification and characterization of the bifunctional aminoadipic semialdehyde synthase with lysine-ketoglutarate reductase and saccharopine dehydrogenase activities. J Biol Chem. 1984 Oct 10;259(19):11643-6. Citation on PubMed
- Sacksteder KA, Biery BJ, Morrell JC, Goodman BK, Geisbrecht BV, Cox RP, Gould SJ, Geraghty MT. Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia. Am J Hum Genet. 2000 Jun;66(6):1736-43. doi: 10.1086/302919. Epub 2000 Apr 20. Citation on PubMed or Free article on PubMed Central
- Saudubray JM, Rabier D. Biomarkers identified in inborn errors for lysine, arginine, and ornithine. J Nutr. 2007 Jun;137(6 Suppl 2):1669S-1672S. doi: 10.1093/jn/137.6.1669S. Citation on PubMed
- Yeganeh M, Auray-Blais C, Maranda B, Sabovic A, DeVita RJ, Lazarus MB, Houten SM. A case of hyperlysinemia identified by urine newborn screening. JIMD Rep. 2023 Oct 22;64(6):440-445. doi: 10.1002/jmd2.12399. eCollection 2023 Nov. Citation on PubMed
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