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URL of this page: https://medlineplus.gov/genetics/condition/x-linked-creatine-deficiency/

X-linked creatine deficiency

Description

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 (ADHD) or autistic behaviors that affect communication and social interaction. They may also experience seizures. Children with X-linked creatine deficiency may grow slower and develop motor skills, such as sitting and walking, later than their peers. 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).

Frequency

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.

Causes

Variants (also known as mutations) in the SLC6A8 gene cause X-linked creatine deficiency. The SLC6A8 gene provides instructions for making a protein that transports a compound called creatine into cells. Creatine is needed for the body to store and use energy properly.

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

Learn more about the gene associated with X-linked creatine deficiency

Inheritance

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 variant 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 variant 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 altered copy of the SLC6A8 gene in each cell have intellectual disability, learning difficulties, or behavioral problems. Other females with one altered copy of the SLC6A8 gene in each cell have no noticeable neurological problems.

Other Names for This Condition

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

Additional Information & Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Clinical Trials

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

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  • Braissant O, Henry H, Beard 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. Citation on PubMed
  • 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. doi: 10.1007/s00439-006-0162-9. Epub 2006 Apr 26. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Erratum In: Semin Neurol. 2014 Sep;34(4):479. Citation on PubMed
  • van de Kamp JM, Betsalel OT, Mercimek-Mahmutoglu S, Abulhoul L, Grunewald 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. Citation on PubMed
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The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.