L-ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY
GATM Sequencing
MITOCHONDRIAL DNA ANALYSIS
Also known as: Creatine Deficiency due to L-Arginine:glycine amidinotransferase

Description:

Creatine and its phosphorylated form play a central role in the energy metabolism of muscle and nerve tissues. There are two steps in the biosynthesis of creatine. L-Arginine:glycine amidinotransferase (AGAT) is the enzyme that catalyzes the transfer of a guanido group from arginine to glycine, forming guanidinoacetic acid, the immediate precursor of creatine, which is the first and committed step in the formation of creatine. AGAT is a 423-amino acid polypeptide including a 37-amino acid signal sequence and is encoded by GATM (AGAT) gene, which is located on 15q15.3 and consists of 9 exons. A homozygous G-A transition, converting a tryptophan codon (TGG) to a stop codon (TAG) at residue 149 (T149X) of the GATM gene, has been reported in 2 sisters, aged 4 and 6 years, with mental retardation who had brain creatine deficiency that was reversible by means of oral creatine supplementation, and had low urinary guanidinoacetate concentrations.

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing
Prenatal diagnosis for known familial mutations

Testing Methodology:

The exons and flanking intronic regions of the GATM gene are PCR amplified and sequenced in both the forward and reverse directions.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc
Requisition form must accompany the specimen. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83891, 83904x18, 83898x9, 83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:

>> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included
>> Prenatal Requisition

References:

1. Humm, A.; Fritsche, E.; Mann, K.; Gohl, M.; Huber, R. : Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue. Biochem. J. 322: 771-776, 1997. PubMed ID : 9148748
2. Bianchi, M. C.; Tosetti, M.; Fornai, F.; Alessandri, M. G.; Cipriani, P.; De Vito, G.; Canapicchi, R. : Reversible brain creatine deficiency in two sisters with normal blood creatine level. Ann. Neurol. 47: 511-513, 2000. PubMed ID : 10762163
3. Item, C. B.; Stockler-Ipsiroglu, S.; Stromberger, C.; Muhl, A.; Alessandri, M. G.; Bianchi, M. C.; Tosetti, M.; Fornai, F.; Cioni, G. : Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am. J. Hum. Genet. 69: 1127-1133, 2001. PubMed ID : 11555793

Test Codes:

Index: 3455
Known Familial Mutation: 3456
Prenatal: 3457