Creatine transporter defect

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Classification according to ICD-10
E72.8 Other specified disorders of amino acid metabolism
ICD-10 online (WHO version 2019)

The creatine transporter defect is a very rare, to the syndromic X-linked mental retardation scoring congenital disorder of creatine transport to the main features mental retardation , seizures and significantly delayed language acquisition .

Synonyms are: SLC6A8 deficiency; X-linked intellectual disability - convulsions - short stature - midface hypoplasia

The first description was made in 2001 by the Dutch doctor Gajja S. Salomons and colleagues.

distribution

The frequency is unknown; more than 150 people have been described to date. The male gender is mainly affected. The inheritance is X-linked - recessive .

root cause

Of the disease are mutations in the SLC6A8 - gene on the X chromosome locus q28, which codes for a transporter Creatine.

In the meantime, further creatine transporter defects have been identified, so that the X-chromosomal inherited disease must be distinguished from it

  • Type II (GAMT deficiency) (Synonym: guanidinoacetate methyltransferase deficiency; GAMT deficiency; Creatine deficiency syndrome Due To GAMT deficiency; CCDS2 ) with mutations in the GAMT gene on chromosome 19 to p13.3, which for the Guanidinoacetate N-methyltransferase encoded .
  • Type III (AGAT deficiency) (Synonym: Arginine: Glycine Amidinotransferase Deficiency; AGAT Deficiency; GATM Deficiency; Creatine Deficiency Syndrome Due To AGAT Deficiency; CCDS3 ) with mutations in the GATM gene on chromosome 15 at q21.q, which represents the L -Arginine: encodes glycine amidinotransferase .

Clinical manifestations

Clinical criteria are:

  • Onset of illness during childhood, usually in the first few years of life
  • intellectual deficit
  • Behavioral problems
  • Seizures
  • severely delayed speech development

In addition, there can be microcephaly , hypoplasia of the midface with a long and narrow face and a prominent chin. Mild neuropsychological impairments can occur in female carriers.

Diagnosis

In urine , an increased allows excretion of creatine prove in the nuclear magnetic resonance spectroscopy of creatine deficiency can be detected in the brain. The diagnosis is confirmed by a human genetic examination .

Differential diagnostics

Other forms of creatine deficiency, such as GAMT deficiency or AGAT deficiency , must be distinguished. under causes.

treatment

In some patients, the high-dose administration of creatine monohydrate, also together with L-arginine and glycine, brought improvements.

literature

  • JM van de Kamp, GM Mancini, PJ Pouwels, OT Betsalel, SJ van Dooren, I. de Koning, ME Steenweg, C. Jakobs, MS van der Knaap, GS Salomons: Clinical features and X-inactivation in females heterozygous for creatine transporter defect. In: Clinical genetics. Vol. 79, No. 3, March 2011, pp. 264-272, doi: 10.1111 / j.1399-0004.2010.01460.x , PMID 20528887 .
  • A. Schulze: Creatine deficiency syndromes. In: Molecular and cellular biochemistry. Vol. 244, No. 1-2, February 2003, pp. 143-150, doi: 10.1023 / A: 1022443503883 . PMID 12701824 . (Review).

Individual evidence

  1. ↑ a b c d e Creatine transporter deficiency, X-linked. In: Orphanet (Rare Disease Database).
  2. ↑ GS Salomons, SJ van Dooren, NM Verhoeven, KM Cecil, WS Ball, TJ Degrauw, C. Jakobs: X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. In: American Journal of Human Genetics . Vol. 68, No. 6, June 2001, pp. 1497-1500, doi: 10.1086 / 320595 , PMID 11326334 , PMC 1226136 (free full text).
  3. ^ Genetics Home Reference
  4. ↑ Cerebral creatine deficiency syndrome 1.  In: Online Mendelian Inheritance in Man . (English)
  5. ↑ Cerebral creatine deficiency syndrome 2.  In: Online Mendelian Inheritance in Man . (English)
  6. ↑ Cerebral creatine deficiency syndrome 3.  In: Online Mendelian Inheritance in Man . (English)
  7. ↑ Guanidinoacetate methyltransferase deficiency. In: Orphanet (Rare Disease Database).
  8. ↑ L-arginine: glycine amidinotransferase deficiency. In: Orphanet (Rare Disease Database).

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