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X-linked creatine deficiency

Reviewed June 2015

What is X-linked creatine deficiency?

X-linked creatine deficiency is an inherited disorder that primarily affects the brain. People with this disorder have intellectual disability, which can range from mild to severe, and delayed speech development. Some affected individuals develop behavioral disorders such as attention deficit hyperactivity disorder or autistic behaviors that affect communication and social interaction. They may also experience seizures. Children with X-linked creatine deficiency may experience slow growth and exhibit delayed development of motor skills such as sitting and walking. Affected individuals tend to tire easily.

A small number of people with X-linked creatine deficiency have additional signs and symptoms including abnormal heart rhythms, an unusually small head (microcephaly), or distinctive facial features such as a broad forehead and a flat or sunken appearance of the middle of the face (midface hypoplasia).

How common is X-linked creatine deficiency?

The prevalence of X-linked creatine deficiency is unknown. More than 150 affected individuals have been identified. The disorder has been estimated to account for between 1 and 2 percent of males with intellectual disability.

What genes are related to X-linked creatine deficiency?

Mutations in the SLC6A8 gene cause X-linked creatine deficiency. The SLC6A8 gene provides instructions for making a protein that transports the compound creatine into cells. Creatine is needed for the body to store and use energy properly.

SLC6A8 gene mutations impair the ability of the transporter protein to bring creatine into cells, resulting in a creatine shortage (deficiency). The effects of creatine deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.

Related Gene(s)

Changes in this gene are associated with X-linked creatine deficiency.

  • SLC6A8

How do people inherit X-linked creatine deficiency?

This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell may or may not cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In most cases of X-linked inheritance, males experience more severe symptoms of the disorder than females. About half of females with one mutated copy of the SLC6A8 gene in each cell have intellectual disability, learning difficulties, or behavioral problems. Other females with one mutated copy of the SLC6A8 gene in each cell have no noticeable neurological problems.

Where can I find information about diagnosis or management of X-linked creatine deficiency?

These resources address the diagnosis or management of X-linked creatine deficiency and may include treatment providers.

  • Gene Review: Creatine Deficiency Syndromes (http://www.ncbi.nlm.nih.gov/books/NBK3794)
  • Genetic Testing Registry: Creatine deficiency, X-linked (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1845862)

You might also find information on the diagnosis or management of X-linked creatine deficiency in Educational resources and Patient support.

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about X-linked creatine deficiency?

You may find the following resources about X-linked creatine deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for X-linked creatine deficiency?

  • creatine transporter defect
  • creatine transporter deficiency
  • SLC6A8 deficiency
  • SLC6A8-related creatine transporter deficiency
  • X-linked creatine deficiency syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about X-linked creatine deficiency?

Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding X-linked creatine deficiency?

attention deficit hyperactivity disorder ; cell ; chromosome ; compound ; creatine ; deficiency ; disability ; gene ; hyperactivity ; hypoplasia ; inheritance ; inherited ; microcephaly ; motor ; mutation ; neurological ; prevalence ; protein ; sex chromosomes ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Béard E, Braissant O. Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem. 2010 Oct;115(2):297-313. doi: 10.1111/j.1471-4159.2010.06935.x. Epub 2010 Aug 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20796169?dopt=Abstract)
  • Braissant O, Henry H, Béard E, Uldry J. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids. 2011 May;40(5):1315-24. doi: 10.1007/s00726-011-0852-z. Epub 2011 Mar 10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21390529?dopt=Abstract)
  • Clark AJ, Rosenberg EH, Almeida LS, Wood TC, Jakobs C, Stevenson RE, Schwartz CE, Salomons GS. X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology. Hum Genet. 2006 Jul;119(6):604-10. Epub 2006 Apr 26. (http://www.ncbi.nlm.nih.gov/pubmed/16738945?dopt=Abstract)
  • Comeaux MS, Wang J, Wang G, Kleppe S, Zhang VW, Schmitt ES, Craigen WJ, Renaud D, Sun Q, Wong LJ. Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes. Mol Genet Metab. 2013 Jul;109(3):260-8. doi: 10.1016/j.ymgme.2013.04.006. Epub 2013 Apr 17. (http://www.ncbi.nlm.nih.gov/pubmed/23660394?dopt=Abstract)
  • Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD. Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases. Mol Genet Metab. 2014 Aug;112(4):259-74. doi: 10.1016/j.ymgme.2014.05.011. Epub 2014 May 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/24953403?dopt=Abstract)
  • Longo N, Ardon O, Vanzo R, Schwartz E, Pasquali M. Disorders of creatine transport and metabolism. Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):72-8. doi: 10.1002/ajmg.c.30292. Epub 2011 Feb 9. (http://www.ncbi.nlm.nih.gov/pubmed/21308988?dopt=Abstract)
  • Nasrallah F, Feki M, Kaabachi N. Creatine and creatine deficiency syndromes: biochemical and clinical aspects. Pediatr Neurol. 2010 Mar;42(3):163-71. doi: 10.1016/j.pediatrneurol.2009.07.015. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20159424?dopt=Abstract)
  • Stockler-Ipsiroglu S, van Karnebeek CD. Cerebral creatine deficiencies: a group of treatable intellectual developmental disorders. Semin Neurol. 2014 Jul;34(3):350-6. doi: 10.1055/s-0034-1386772. Epub 2014 Sep 5. Review. Erratum in: Semin Neurol. 2014 Sep;34(4):479. (http://www.ncbi.nlm.nih.gov/pubmed/25192512?dopt=Abstract)
  • van de Kamp JM, Betsalel OT, Mercimek-Mahmutoglu S, Abulhoul L, Grünewald S, Anselm I, Azzouz H, Bratkovic D, de Brouwer A, Hamel B, Kleefstra T, Yntema H, Campistol J, Vilaseca MA, Cheillan D, D'Hooghe M, Diogo L, Garcia P, Valongo C, Fonseca M, Frints S, Wilcken B, von der Haar S, Meijers-Heijboer HE, Hofstede F, Johnson D, Kant SG, Lion-Francois L, Pitelet G, Longo N, Maat-Kievit JA, Monteiro JP, Munnich A, Muntau AC, Nassogne MC, Osaka H, Ounap K, Pinard JM, Quijano-Roy S, Poggenburg I, Poplawski N, Abdul-Rahman O, Ribes A, Arias A, Yaplito-Lee J, Schulze A, Schwartz CE, Schwenger S, Soares G, Sznajer Y, Valayannopoulos V, Van Esch H, Waltz S, Wamelink MM, Pouwels PJ, Errami A, van der Knaap MS, Jakobs C, Mancini GM, Salomons GS. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. J Med Genet. 2013 Jul;50(7):463-72. doi: 10.1136/jmedgenet-2013-101658. Epub 2013 May 3. (http://www.ncbi.nlm.nih.gov/pubmed/23644449?dopt=Abstract)
  • van de Kamp JM, Mancini GM, Salomons GS. X-linked creatine transporter deficiency: clinical aspects and pathophysiology. J Inherit Metab Dis. 2014 Sep;37(5):715-33. doi: 10.1007/s10545-014-9713-8. Epub 2014 May 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/24789340?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2015
Published: August 24, 2015