MNGIE (MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY)
Thymidine Phosphorylase (TP), TYMP Sequencing
MITOCHONDRIAL DNA ANALYSIS

Description:

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase (TP) gene, TYMP. TP protein catalyzes phosphorolysis of thymidine to thymine and deoxyribose-1-phosphate, a salvage pathway involved in the maintenance of mitochondrial dNTP pools. Deficiency of TP causes the accumulation of thymidine. Both the enzyme activity in leukocytes and the elevated levels of thymidine in plasma can be measured (please see Thymidine Determination). The unbalanced mitochondrial deoxynucleotide pools result in mitochondrial DNA depletion, multiple deletions, or both in affected tissues. Clinical features of the disease usually occur between the second and the fifth decade of life. Gastrointestinal dysmotility is the most prominent clinical feature. Cerebral leukodystrophy is characteristic. Others include ptosis, progressive external ophthalmoplegia, cachexia, peripheral neuropathy, and myopathy.

Reasons for Referral:

To confirm the diagnosis of MNGIE.
To confirm the diagnosis of mitochondrial DNA depletion and/or multiple deletion caused by mutations in thymidine phosphorylase gene.

Testing Methodology:

The exons and flanking intron regions of the TYMP gene are PCR amplified and sequenced.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc

Turnaround Time:

Index: 3 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index:83904x8, 83898x4, 83912, 83891, 83894x2
Known Familial Mutation: 83904x4, 83912, 83898x2, 83891, 83894x2

Shipping Information

Forms:

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

References:

1. Nishino I, Spinazzola A, Hirano M. (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283: 689-692.
2. Nishino I, Spinazzola A, Papadimitriou A, Hammans S, Steiner I, Hahn CD, Connolly AM, Verloes A, Guimaraes J, Maillard I, Hamano H, Donati MA, Semrad CE, Russell JA, Andreu AL, Hadjigeorgiou GM, Vu TH, Tadesse S, Nygaard TG, Nonaka I, Hirano I, Bonilla E, Rowland LP, DiMauro S, Hirano M. (2000) Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann. Neurol. 47: 792-800.

Test Codes:

Index: 3060
Known Familial Mutation: 3061
Prenatal: 3062