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Hyperlysinemia
URL of this page: https://medlineplus.gov/genetics/condition/hyperlysinemia/

Hyperlysinemia

Description

Hyperlysinemia is an inherited condition that is characterized by elevated blood levels of lysine, which is one of the building blocks (amino acids) of proteins. Amino acids are not stored in the body and must be broken down when they are no longer needed. When the body's ability to break down lysine is impaired, lysine can build up and cause hyperlysinemia. Hyperlysinemia is classified as either type I or type II, depending on which steps of lysine breakdown are interrupted. 

The signs and symptoms of hyperlysinemia can vary widely, even among members of the same family. The features that have been reported in people with hyperlysinemia have included short stature, speech and language delays, intellectual disabilities, behavioral abnormalities, abnormal muscle stiffness (spasticity), and seizures. However, some researchers have suggested that as many as half of all people with hyperlysinemia are asymptomatic, which means that they do not have any signs or symptoms of the disorder. These people may not even be aware that they have the condition.

Because the signs and symptoms of hyperlysinemia can vary and because hyperlysinemia is very rare, it is difficult for researchers to determine whether these features are caused by the condition itself or by other factors. 

People with a condition called 2,4-dienoyl-CoA reductase (DECR) deficiency may also have hyperlysinemia. Additional features of DECR deficiency may include an inability to grow and gain weight as expected (failure to thrive), developmental delays, abnormal brain function (encephalopathy), and eye abnormalities such as degeneration of the nerves that carry information from the eyes to the brain (optic atrophy).

Frequency

The exact incidence of hyperlysinemia is unknown. Researchers have suggested that hyperlysinemia type I affects approximately 1 in 411,000 newborns. Hyperlysinemia type II is less common than type I.

Causes

Variants (also called mutations) in the AASS gene cause both types of hyperlysinemia. The AASS gene provides instructions for making an enzyme called alpha-aminoadipic semialdehyde synthase. This enzyme performs two functions during the breakdown of lysine. First, the enzyme converts lysine to a molecule called saccharopine. This same enzyme also converts saccharopine to a molecule called alpha-aminoadipic semialdehyde.

The variants in the AASS gene that impair both the breakdown of lysine and the breakdown of saccharopine cause hyperlysinemia type I. The AASS gene variants that mostly impair the breakdown of saccharopine cause hyperlysinemia type II. Both type I and type II result in elevated levels of lysine in the blood. People with type II may also have elevated levels of saccharopine in the urine.

Researchers are not sure why some people with hyperlysinemia have signs and symptoms, while others are asymptomatic. It is also unclear how higher levels of lysine in the blood cause the signs and symptoms seen in some people with hyperlysinemia. More research is needed to fully understand the effects of hyperlysinemia on the body.

Learn more about the gene associated with Hyperlysinemia

Inheritance

Hyperlysinemia is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • Alpha-aminoadipic semialdehyde synthase deficiency
  • Familial hyperlysinemia
  • Lysine alpha-ketoglutarate reductase deficiency
  • Saccharopine dehydrogenase deficiency
  • Saccharopinuria

Additional Information & Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

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  • 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
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  • 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
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  • van Gelderen HH, Teijema HL. Hyperlysinaemia. Harmless inborn error of metabolism? Arch Dis Child. 1973 Nov;48(11):892-5. doi: 10.1136/adc.48.11.892. No abstract available. 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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