TYMP

Mitochondrial DNA Depletion Syndrome 1

Clinical Characteristics

Ocular Features:

Progressive external ophthalmoplegia has an adult onset, usually in the late second or early third decade of life. Ptosis is commonly present as well.

Systemic Features:

This condition has been called a mitochondrial neurogastrointestinal encephalopathy (MNGIE). Gastrointestinal problems are among the most disabling with poor absorption of foodstuffs leading to weight loss, marked cachexia, and chronic malnutrition. Added to this are gastroparesis, constipation, vomiting, and intermittent diarrhea with abdominal pain. Many individuals develop diverticulosis and diverticulitis that may lead to intestinal perforations. The combined intestinal dysfunctions can lead to signs of intestinal pseudoobstruction.

Many patients have a progressive sensorineural hearing loss. Leukoencephalopathy, sensorimotor peripheral neuropathy, and sometimes mild proximal limb weakness may be present.

Genetics

Homozygous and compound heterozygous mutations in the TYMP gene (22q13.33) are responsible for this autosomal recessive disorder. This nuclear gene is active in the maintainence of mitochondrial DNA. When the gene is dysfunctional, the mitochondria can be depleted to a variable extent and they may contain multiple deletions and point mutations.

Pedigree:

Autosomal recessive

Treatment

Treatment Options:

There is no effective treatment for the overall condition. Nutritionists can provide important advice on diet to maintain good nutrition. Regular monitoring by gastroenterologists is important. Perforations of the bowels require prompt surgical repair.

References

Article Title:

Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion

Giordano C, Sebastiani M, De Giorgio R, Travaglini C, Tancredi A, Valentino ML, Bellan M, Cossarizza A, Hirano M, d'Amati G, Carelli V. Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion. Am J Pathol. 2008 Oct;173(4):1120-8.

PubMed ID:

18787099

Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations

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. Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann Neurol. 2000 Jun;47(6):792-800.

PubMed ID:

10852545

You are here

Search For A Disorder