Pitfalls in diagnosing mitochondrial neurogastrointestinal encephalomyopathy

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase and is characterized by external ophthalmoparesis, gastrointestinal dysmotility, leukoencephalopathy, and neuropathy. The availability of new therapeutic options (peritoneal dialysis, allogeneic stem cell transplantation, enzyme replacement) makes it necessary to diagnose the disease early, which is not always achieved due to the difficulty in recognizing this disorder, especially in case of atypical presentation. We describe three MNGIE patients with atypical onset of the disease. In the first patient the main symptoms were long-standing chronic fever, recurrent acute migrant arthritis, and gastrointestinal disorders mimicking autoimmune or inflammatory intestinal diseases; the second patient complained only of exercise intolerance and muscle cramps, and the third patient had a CIDP-like polyneuropathy. This study stresses the insidious heterogeneous clinical onset of some cases of MNGIE, expands the spectrum of the phenotype, and suggests considering MNGIE in the differential diagnosis of enteropathic arthritis, isolated exercise intolerance, and inflammatory polyneuropathies not responsive to the usual treatment. A better understanding of the clinical heterogeneity of MNGIE is necessary in order to diagnose atypical cases and promote early diagnosis, which is now absolutely necessary in view of the new available therapies.

Hereditary and inflammatory neuropathies: a review of reported associations, mimics and misdiagnoses

“…However, the clinical picture as detailed appeared highly suggestive of MNGIE with electrophysiology and histopathology being compatible with CIDP. Filosto et al 74 also described a male patient with distal paraesthesiae, and global lower limb weakness without gastrointestinal symptoms but with accompanying ptosis, extraocular weakness and deafness. Electrophysiology showed demyelination confirmed histologically and CSF protein was 3.17 g/L.…”

Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement

“…The patient was reported previously by Filosto et al 7 An initial diagnosis of an inflammatory polyneuropathy was made; corticosteroids, immunoglobulins, and cyclophosphamide were administered without clinical benefit. At age 26 years, a compound heterozygous TYMP mutation was demonstrated.…”

The Role of Brain MRI in Mitochondrial Neurogastrointestinal Encephalomyopathy

“…Clinical findings of these patients have already been reported 10,27 ; clinical, biochemical and molecular data are summarized in Table 1.…”

“…This implies that the diagnosis should be made as early as possible to prevent organ damage and to maximize the benefits of treatments [28][29][30] . White matter alterations in supratentorial areas can be considered a hallmark of MNGIE because they are present in patients with both classical phenotype and atypical presentation 3,6,[10][11][12] . Therefore, if a clinical suspicion emerges, MRI often addresses the correct diagnosis.…”

“…entations have been described and frequent misdiagnosis such as anorexia nervosa, inflammatory bowel disease, superior mesenteric artery syndrome, Whipple disease, chronic intestinal pseudo-obstruction, chronic inflammatory demyelinating polyneuropathy (CIDP) and Charcot Marie Tooth (CMT) disease have been reported [7][8][9][10] . Leukoencephalopathy is a hallmark of MNGIE, so far reported in all patients 3,6 .…”