Mitochondrial neurogastrointestinal
encephalopathy (MNGIE) is an autosomal recessive mitochondriopathy caused by loss-of-function mutations in the
thymidine phosphorylase gene. The disease leads to premature death and is characterized by gastrointestinal dysmotility and
cachexia,
external ophthalmoplegia, a sensorimotor neuropathy, and
leukoencephalopathy.
Bone marrow transplantation (BMT) is the only potentially curative treatment that can achieve a sustained biochemical correction of the metabolic imbalances.We report a 23-year-old male homozygous for the c.866A > C, p.Glu289Ala mutation of the TYMP gene, who presented with
fatty liver and
cachexia. Laboratory examinations were unremarkable except for increased
transaminase activities. Grade II
fibrosis and steatosis was found in an initial and a follow-up liver biopsy 4 years later. Myeloablative conditioning and BMT was performed 10 years after initial presentation due to the progressive
weight loss and
polyneuropathy. Pre-
transplant liver staging was normal except for an elevated transient elastography of 31.6 kPa. Severe
ascites developed after
transplantation and liver function deteriorated progressively to
liver failure. Despite engraftment on day +15, the patient died on day +18 from
liver failure. Autopsy revealed micronodular
liver cirrhosis, and postmortem diagnosis of
acute-on-chronic liver failure was done.This case illustrates the difficulties and importance of diagnosing
liver cirrhosis in MNGIE. Before BMT, patients must be carefully evaluated by transient elastography, liver biopsy, or assessment of hepatic venous pressure gradient. In patients with
liver cirrhosis, further studies should evaluate if
liver transplantation may be an alternative to BMT. Considerable amounts of
thymidine phosphorylase are expressed in liver tissue which may prevent accumulation of toxic metabolites.