Mitochondrial Neurogastrointestinal Encephalomyopathy Treated with Stem Cell Transplantation: A Case Report and Review of Literature

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder. The mutation in the ECGF1 gene causes severe deficiency of thymidine phosphorylase (TP), which in turn increases thymidine and deoxyuridine in the blood, serum, and tissue. The toxic levels of these products cause malfunction of the mitochondrial respiratory chain and mitochondrial DNA. Commonly, patients become symptomatic between 15 and 20 years of age (range 5 months to 35 years). The most commonly affected systems are gastrointestinal, followed by ocular, and nervous system. The disease is often fatal; high mortality rate is reported between 20 and 40 years of age. Treatment modalities that can increase thymidine phosphorylase activity and decrease thymidine and deoxy-uridine have shown symptomatic improvements in patients with MNGIE. Platelet transfusion, hemodialysis, peritoneal dialysis or allogeneic hematopoietic stem cell transplantation (HSCT) have been tried. The survival and long-term benefits of these measures are still not clear. Engrafted patients after stem cell transplantation have showed improvements in serum thymidine and deoxyuridine. We are reporting a case of MNGIE from Saudi Arabia, who underwent allogeneic hematopoietic stem cell transplantation. No MNGIE case has been previously reported from Saudi Arabia or the Gulf Arab countries. From the available literature, so far only 11 patients with MNGIE have undergone stem cell transplantation.

Mitochondrial diseases caused by toxic compound accumulation: from etiopathology to therapeutic approaches

“…The disease locus was mapped in 1998 to chromosome 22, where mutations in the ECGF1 gene (today known as TYMP ) were identified as the culprits in MNGIE (Nishino et al , 1999 ). Since then, more than 140 additional individuals with MNGIE have been described (Hirano et al , 2012 ; Peedikayil et al , 2015 ). TYMP is expressed in most human tissues and organs, but with little or no expression in gallbladder, aorta, muscle, fat, and kidney (Matsukawa et al , 1996 ).…”

“…To date, twelve MNGIE patients have been treated with allogeneic HSCT (Peedikayil et al , 2015 ), with evidence of rapid restoration of enzyme activity together with a reduction or disappearance of plasma dThd and dUrd in patients who engrafted. There remain, however, several limitations: (1) limited tolerance of the patients for transplant-related complications, (2) low engraftment rates, and (3) risk of graft rejection, which mandates for adequate conditioning and immunosuppression.…”

Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment

“…To evaluate the gastrointestinal symptoms, a range of diagnostic modalities are used and include abdominal ultrasound, abdominal imaging (X-ray and computed tomography), upper gastrointestinal tract contrast radiography, esophagogastroduodenoscopy, sigmoidoscopy, colonoscopy, liquid phase scintigraphy, antroduodenal manometry, biopsy and histopathological examination [44][45][46] . These assessments often reveal hepatomegaly, hepatosteatosis, dilatation and thickening of the stomach and small intestine, jejunum diverticulosis, reduced gastroduodenal motility and transit, decreased lower oesophageal sphincter pressure, a low amplitude of oesophageal contractions, gastroparesis, reflux oesophagitis, panagastritis, non-specific chronic inflammation in the small intestine and foamy cells in the intestinal wall [21,23,30,[47][48][49][50][51][52][53][54][55] .…”

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“…Case 1 was previously presented. 5 A 26-year-old male patient had symptoms of watery diarrhea and abdominal pain over a period of 15 years. This was associated with difficulty in swallowing on a few occasions.…”