Let's talk about MNGIE

About MNGIE

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) disease is a condition that affects several parts of the body, particularly the digestive and nervous systems.1 Many MNGIE patients experience:

  • Weight and muscle loss
  • Issues with the digestive track, including episodes of abdominal pain and intestinal blockage
  • Drooping of the eyelids and tingling sensations in the limbs
  • A longstanding, chronic, progressive condition with frequent misdiagnosis

Genetics & Biochemistry

MNGIE is caused by mutations in the TYMP gene. These mutations result in the insufficient activity of an enzyme called thymidine phosphorylase (TP) in MNGIE patients.2

Healthy Cell
MNGIE Cell
Cell
Mitochondria
TP Enzyme
Thymidine

MNGIE is an autosomal recessive disease, which means both parents must have at least 1 copy of a genetic mutation of the TYMP gene in order to have a child with MNGIE.2

Parents can either have MNGIE or be carriers of the genetic mutation. Carriers are people who are healthy, but can still pass on their genetic mutation. Both female and male children can inherit MNGIE.

If 2 parents who are carriers of MNGIE have a child, there is a:

  • 25% chance the child neither inherits MNGIE nor is a carrier
  • 50% chance the child is a carrier of the genetic mutation (like the parents)  
  • 25% chance the child will inherit MNGIE


Parent with TYMP gene mutation

Parent with TYMP gene mutation
25%

Child without MNGIE or TYMP gene mutation

Offspring will not develop MNGIE

50%

Child without MNGIE but carries TYMP gene mutation

Can pass on TYMP gene mutation. Offspring might develop MNGIE

25%

Child with MNGIE

Can pass on TYMP gene mutation. Offspring might develop MNGIE

Parent with TYMP gene mutation

Parent with TYMP gene mutation
25% chance

Child without MNGIE or TYMP gene mutation

Offspring will not develop MNGIE

50% chance

Child without MNGIE but carries TYMP gene mutation

Can pass on TYMP gene mutation. Offspring might develop MNGIE

25% chance

Child with MNGIE

Can pass on TYMP gene mutation. Offspring might develop MNGIE

Symptoms

Based on an analysis of over 100 patients, the mean age at onset is approximately 18 years (5 months-35 years), although diagnosis is possible both earlier and later in life.1

The typical symptoms are both gastrointestinal and neurological.1,3

Symptoms are cumulative and progressive. Neurological manifestations may be subtle and underestimated by patients and healthcare providers and therefore recognized late.

When gastrointestinal symptoms are typically the first manifestation, the diagnosis and consequently the appropriate treatment may be significantly delayed because of misdiagnosis (anorexia, Crohn’s disease, etc.).

Gastrointestinal

Symptoms can include abdominal pain or cramps, vomiting/nausea, diarrhea, abnormal bowel sounds, intestinal pseudo-obstruction, feeling full early, delayed stomach emptying, difficulty swallowing, etc.

Weight Loss

Most patients experience thinness during the course of disease.

Neurological

Symptoms can include drooping of the upper eyelids, weakness of muscles that move the eyes, damage to the peripheral nerves causing abnormal sensations and weakness in the feet and hands.

Diagnosis

To confirm the diagnosis of MNGIE3:

  • Thymidine and deoxyuridine test: Increased concentration of these metabolites in blood plasma
  • Thymidine phosphorylase activity test: Thymidine phosphorylase activity is severely reduced in blood (buffy coat)
  • Brain MRI: White matter changes on magnetic resonance imaging (MRI) of the brain
  • Genetic sequencing: TYMP gene sequencing showing homozygous or compound heterozygous mutations

Thymidine Test

A blood sample is taken to measure the levels of two metabolites, thymidine and deoxyuridine. Elevated levels of plasma thymidine and deoxyuridine are sufficient to make the diagnosis of MNGIE.

Thymidine Phosphorylase Activity Test

A blood sample is taken to measure thymidine phosphorylase activity. Low thymidine phosphorylase activity can support a diagnosis of MNGIE.

Brain MRI

In MNGIE patients, an MRI of the brain typically shows abnormal white matter, caused by a brain condition called leukoencephalopathy. This finding supports a diagnosis of MNGIE.

Gene Sequencing

A blood, saliva or cheek swab sample is taken for genetic sequencing to see if there are any mutations in the TYMP gene. Mutations in the TYMP gene can confirm a diagnosis of MNGIE.

Ready to Connect?

MNGIE Clinical Trials

For a list of clinical trials for MNGIE patients, please visit ClinicalTrials.gov.

Clinical Trials List

Resources

Below are some resources with information about MNGIE and mitochondrial diseases.

United Mitochondrial Disease Foundation (UMDF)

Nonprofit to promote research and education for the diagnosis, treatment, and cure of mitochondrial disorders and to provide support to affected individuals and families

International Mito-Patients

Network of national patient organizations involved in mitochondrial disease

The Lily Foundation

UK nonprofit dedicated to fighting mitochondrial disease

MitoAction

Nonprofit organization focused on improving quality of life for children and adults with mitochondrial disease
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News

The latest news on MNGIE

December 11th, 2019

Mitochondrial Medicine Conference 2019 – Wellcome Trust

The Mitochondrial Medicine conference aims to bridge the gap between our current understanding of the mechanisms and processes that go awry in mitochondrial disease and the novel approaches being developed to treat them.
Read More
November 8th, 2019

MITO2019 Annual Meeting – mitoNET and MitoCanada Foundation

MITO2019 is the annual meeting and cornerstone program for mitoNET and the MitoCanada Foundation. The conference features patient engagement, keynote presentations, a parallel symposia program and rapid communications sessions.
Read More
March 30th, 2019

Consensus Conference on the Diagnosis and Treatment of MNGIE, Bologna

The consensus conference on the diagnosis and treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) was held in Bologna on the 30th and 31st of March.
Read More
More News

References