FATAL INFANTILE LACTIC ACIDOSIS with mtDNA DEPLETION
SUCLG1 Sequencing
MITOCHONDRIAL DNA ANALYSIS
See also: SUCLA2 Sequencing; Thymidine Kinase TK2 Sequencing; RRM2B Sequencing

Description:

The SUCLG1 gene encodes the alpha-subunit of the GDP-forming succinate-CoA ligase (alternative name: succinyl-CoA synthetase (SCS)). SCS is a mitochondrial matrix enzyme catalyzing the reversible synthesis of succinyl-CoA and either ADP or GDP to succinate and either ATP of GTP, depending on which beta-subunit is present, in the Krab cycle. This dimeric enzyme consists of one alpha subunit and one of two beta units encoded either by SUCLA2 (test code 3375) (ATP/ADP specific) or SUCLG2 (GTP/GDP specific). Thus, the beta subunit determines substrate specificity for either the GTP-dependent or ATP-dependent reactions. One mutation of 2-bp homozygous deletion in SUCLG1 has been identified in a consanguineous Pakistani family with fatal infantile lactic acidosis and mitochondrial DNA depletion. The clinical symptoms of SUCLG1 mutation are similar to those of SUCLA2 mutations. Elevated levels of lactate, pyruvate, methylmalonate and methylcitrate in urine suggest a deficiency of SCS. The human SUCLG1 gene is located at 2p11.2 and contains 9 coding exons encoding 333 amino acids.

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 SUCLG1 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
>> Prenatal Requisition

References:

1. James M, Man N, Edwards YH, Morris GE. The molecular basis for cross-reaction of an anti-dystrophin antibody with alpha-actinin. Biochim. Biophys. Acta 1360: 169-176, 1997.
2. Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F. Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am J Hum Genet. 81(2):383-7, 2007

Test Codes:

Index: 3390
Known Familial Mutation: 3391
Prenatal: 3392