A Retrospective Natural History Study of Subjects Affected by Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE, ORPHA#298; OMIM#603041) is an autosomal recessive disease caused by loss-of-function mutations in TYMP, the gene encoding the enzyme thymidine phosphorylase (TP).

Epidemiology and disease course:

MNGIE is an ultra-rare disease with limited available epidemiological studies. Most of the knowledge about disease course of MNGIE derives from single centre experiences, case reports, and two retrospective observational cohort studies published so far. MNGIE is a chronic debilitating and ultimately fatal condition, with average age of diagnosis around 18 years. Depending on the studied cohort, the majority of patients are thought not to survive beyond 40 years.

The earliest and most debilitating signs of MNGIE are gastrointestinal (GI), with a wide range of symptoms reported (including abdominal pain and cramps, nausea or vomiting, diarrhoea or constipation, pseudo-obstruction and gastroparesis, dysphagia, malabsorption and cachexia). GI symptoms occur in almost all reported patients. Other typical symptoms are primary mitochondrial myopathy with weakness of the eye muscles (chronic progressive external ophthalmoplegia and ptosis) in almost all patients, and peripheral neuropathy also found in most patients. All patients have leukoencephalopathy on brain magnetic resonance imaging (MRI), but this is thought to remain asymptomatic.

A wide range of other clinical features have been reported in retrospective cohort studies, and through many additional case reports in the literature. However, a comprehensive review of clinical and laboratory data from all reported and unpublished patients is lacking, and many aspects of the disease remain poorly understood.