Format

Send to:

Choose Destination

Links from PubMed

Arginine:glycine amidinotransferase deficiency(L-Arginine)

MedGen UID:
436367
Concept ID:
C2675179
Disease or Syndrome
Synonyms: AGAT deficiency; CEREBRAL CREATINE DEFICIENCY SYNDROME 3; CREATINE DEFICIENCY SYNDROME DUE TO AGAT DEFICIENCY; Creatine Deficiency Syndromes; GATM DEFICIENCY; L-Arginine; L-Arginine:Glycine Amidinotransferase Deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Cerebral creatine deficiency syndrome 3 (702440000); Arginine:glycine amidinotransferase deficiency (702440000); L-arginine:glycine amidinotransferase deficiency (702440000); Creatine deficiency syndrome due to arginine:glycine amidinotransferase deficiency (702440000)
 
Gene (location): GATM (15q21.1)
OMIM®: 612718
Orphanet: ORPHA35704

Disease characteristics

Excerpted from the GeneReview: Creatine Deficiency Syndromes
The cerebral creatine deficiency syndromes (CCDS), inborn errors of creatine metabolism, include the two creatine biosynthesis disorders, guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CRTR) deficiency. Intellectual disability and seizures are common to all three CCDS. The majority of individuals with GAMT deficiency have a behavior disorder that can include autistic behaviors and self-mutilation; about 40% have movement disorder. Onset is between ages three months and three years. Only 14 individuals with AGAT deficiency have been reported. The phenotype of CRTR deficiency in affected males ranges from mild intellectual disability and speech delay to severe intellectual disability, seizures, movement disorder and behavior disorder; age at diagnosis ranges from two to 66 years. Clinical phenotype of females heterozygous for CRTR deficiency ranges from asymptomatic to severe phenotype resembling male phenotype. [from GeneReviews]
Authors:
Saadet Mercimek-Mahmutoglu  |  Gajja S Salomons   view full author information

Additional descriptions

From OMIM
Cerebral creatine deficiency syndrome-3 is an autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain (Schulze, 2003). Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. Oral creatine supplementation can offer symptom improvement (summary by Edvardson et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of cerebral creatine deficiency syndrome, see CCDS1 (300352).  http://www.omim.org/entry/612718
From GHR
Arginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. People with this disorder have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviors that affect communication and social interaction. They may experience seizures, especially when they have a fever.Children with arginine:glycine amidinotransferase deficiency may not gain weight and grow at the expected rate (failure to thrive), and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily.  https://ghr.nlm.nih.gov/condition/arginineglycine-amidinotransferase-deficiency

Clinical features

Organic aciduria
MedGen UID:
66037
Concept ID:
C0241775
Finding
Excretion of non-amino organic acids in urine.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Sign or Symptom
A degree of language development that is significantly below the norm for a child of a specified age.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Cognitive delay
MedGen UID:
351243
Concept ID:
C1864897
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Autism
MedGen UID:
504569
Concept ID:
CN000674
Finding
Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV).
Organic aciduria
MedGen UID:
66037
Concept ID:
C0241775
Finding
Excretion of non-amino organic acids in urine.
Abnormality of creatine metabolism
MedGen UID:
866482
Concept ID:
C4020731
Finding
An anomaly of the concentration or homeostasis of creatine. Creatine is a derivative of glycine having methyl and amidino groups attached to the nitrogen. Creatine is naturally produced from amino acids, primarily in liver and kidney, and acts as an energy source for cells, primarly for muscle cells.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Arginine:glycine amidinotransferase deficiency in Orphanet.

Recent clinical studies

Etiology

Kayacelebi AA, Langen J, Weigt-Usinger K, Chobanyan-Jürgens K, Mariotti F, Schneider JY, Rothmann S, Frölich JC, Atzler D, Choe CU, Schwedhelm E, Huneau JF, Lücke T, Tsikas D
Amino Acids 2015 Sep;47(9):1893-908. Epub 2015 Jun 2 doi: 10.1007/s00726-015-2012-3. [Epub ahead of print] PMID: 26031828
Clark JF, Cecil KM
Pediatr Res 2015 Mar;77(3):398-405. Epub 2014 Dec 18 doi: 10.1038/pr.2014.203. [Epub ahead of print] PMID: 25521922
Atzler D, Schwedhelm E, Choe CU
Curr Opin Clin Nutr Metab Care 2015 Jan;18(1):83-8. doi: 10.1097/MCO.0000000000000123. PMID: 25474016
Comeaux MS, Wang J, Wang G, Kleppe S, Zhang VW, Schmitt ES, Craigen WJ, Renaud D, Sun Q, Wong LJ
Mol Genet Metab 2013 Jul;109(3):260-8. Epub 2013 Apr 17 doi: 10.1016/j.ymgme.2013.04.006. [Epub ahead of print] PMID: 23660394
Davids M, Ndika JD, Salomons GS, Blom HJ, Teerlink T
FEBS Lett 2012 Oct 19;586(20):3653-7. Epub 2012 Aug 29 doi: 10.1016/j.febslet.2012.08.020. [Epub ahead of print] PMID: 23010440

Diagnosis

Stockler-Ipsiroglu S, Apatean D, Battini R, DeBrosse S, Dessoffy K, Edvardson S, Eichler F, Johnston K, Koeller DM, Nouioua S, Tazir M, Verma A, Dowling MD, Wierenga KJ, Wierenga AM, Zhang V, Wong LJ
Mol Genet Metab 2015 Dec;116(4):252-9. Epub 2015 Oct 17 doi: 10.1016/j.ymgme.2015.10.003. [Epub ahead of print] PMID: 26490222
Clark JF, Cecil KM
Pediatr Res 2015 Mar;77(3):398-405. Epub 2014 Dec 18 doi: 10.1038/pr.2014.203. [Epub ahead of print] PMID: 25521922
Tran C, Yazdanpanah M, Kyriakopoulou L, Levandovskiy V, Zahid H, Naufer A, Isbrandt D, Schulze A
Clin Chim Acta 2014 Sep 25;436:160-8. Epub 2014 May 28 doi: 10.1016/j.cca.2014.05.007. [Epub ahead of print] PMID: 24877651
Ndika JD, Johnston K, Barkovich JA, Wirt MD, O'Neill P, Betsalel OT, Jakobs C, Salomons GS
Mol Genet Metab 2012 May;106(1):48-54. Epub 2012 Jan 27 doi: 10.1016/j.ymgme.2012.01.017. [Epub ahead of print] PMID: 22386973
Verhoeven NM, Schor DS, Roos B, Battini R, Stöckler-Ipsiroglu S, Salomons GS, Jakobs C
Clin Chem 2003 May;49(5):803-5. PMID: 12709373

Therapy

Stockler-Ipsiroglu S, Apatean D, Battini R, DeBrosse S, Dessoffy K, Edvardson S, Eichler F, Johnston K, Koeller DM, Nouioua S, Tazir M, Verma A, Dowling MD, Wierenga KJ, Wierenga AM, Zhang V, Wong LJ
Mol Genet Metab 2015 Dec;116(4):252-9. Epub 2015 Oct 17 doi: 10.1016/j.ymgme.2015.10.003. [Epub ahead of print] PMID: 26490222
Kayacelebi AA, Langen J, Weigt-Usinger K, Chobanyan-Jürgens K, Mariotti F, Schneider JY, Rothmann S, Frölich JC, Atzler D, Choe CU, Schwedhelm E, Huneau JF, Lücke T, Tsikas D
Amino Acids 2015 Sep;47(9):1893-908. Epub 2015 Jun 2 doi: 10.1007/s00726-015-2012-3. [Epub ahead of print] PMID: 26031828
Ndika JD, Johnston K, Barkovich JA, Wirt MD, O'Neill P, Betsalel OT, Jakobs C, Salomons GS
Mol Genet Metab 2012 May;106(1):48-54. Epub 2012 Jan 27 doi: 10.1016/j.ymgme.2012.01.017. [Epub ahead of print] PMID: 22386973
Verma A
Neurology 2010 Jul 13;75(2):186-8. doi: 10.1212/WNL.0b013e3181e7cabd. PMID: 20625172
Item CB, Stöckler-Ipsiroglu S, Stromberger C, Mühl A, Alessandrì MG, Bianchi MC, Tosetti M, Fornai F, Cioni G
Am J Hum Genet 2001 Nov;69(5):1127-33. Epub 2001 Sep 10 doi: 10.1086/323765. [Epub ahead of print] PMID: 11555793Free PMC Article

Prognosis

Clark JF, Cecil KM
Pediatr Res 2015 Mar;77(3):398-405. Epub 2014 Dec 18 doi: 10.1038/pr.2014.203. [Epub ahead of print] PMID: 25521922
Braissant O, Henry H
J Inherit Metab Dis 2008 Apr;31(2):230-9. Epub 2008 Apr 4 doi: 10.1007/s10545-008-0826-9. [Epub ahead of print] PMID: 18392746

Clinical prediction guides

Tran C, Yazdanpanah M, Kyriakopoulou L, Levandovskiy V, Zahid H, Naufer A, Isbrandt D, Schulze A
Clin Chim Acta 2014 Sep 25;436:160-8. Epub 2014 May 28 doi: 10.1016/j.cca.2014.05.007. [Epub ahead of print] PMID: 24877651
Braissant O, Henry H
J Inherit Metab Dis 2008 Apr;31(2):230-9. Epub 2008 Apr 4 doi: 10.1007/s10545-008-0826-9. [Epub ahead of print] PMID: 18392746

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center