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Myoneural gastrointestinal encephalopathy syndrome(MTDPS1)

MedGen UID:
167876
Concept ID:
C0872218
Disease or Syndrome
Synonyms: MITOCHONDRIAL DNA DEPLETION SYNDROME 1 (MNGIE TYPE); Mitochondrial neurogastrointestinal encephalomyopathy syndrome; Mitochondrial Neurogastrointestinal Encephalopathy Disease; Mitochondrial neurogastrointestinal encephalopathy syndrome; MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOPATHY SYNDROME, TYMP-RELATED; MNGIE syndrome; MNGIE, TYMP-RELATED; MTDPS1; Myoneurogastrointestinal encephalopathy syndrome; Oculogastrointestinal muscular dystrophy; POLG-Related Disorders; POLIP SYNDROME; POLYNEUROPATHY, OPHTHALMOPLEGIA, LEUKOENCEPHALOPATHY, AND INTESTINAL PSEUDOOBSTRUCTION; Thymidine phosphorylase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
 
Genes (locations): POLG (15q26.1); TYMP (22q13.33)
OMIM®: 603041

Disease characteristics

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is characterized by progressive gastrointestinal dysmotility and cachexia manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain and/or distention, and diarrhea; ptosis/ophthalmoplegia or ophthalmoparesis; hearing loss; and demyelinating peripheral neuropathy manifesting as paresthesias (tingling, numbness, and pain) and symmetric and distal weakness more prominently affecting the lower extremities. The order in which manifestations appear is unpredictable. Onset is usually between the first and fifth decades; in about 60% of individuals, symptoms begin before age 20 years. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
John M Shoffner   view full author information

Additional descriptions

From OMIM
Mitochondrial DNA depletion syndrome-1 (MTDPS1) is an autosomal recessive progressive multisystem disorder clinically characterized by onset between the second and fifth decades of life of ptosis, progressive external ophthalmoplegia (PEO), gastrointestinal dysmotility (often pseudoobstruction), cachexia, diffuse leukoencephalopathy, peripheral neuropathy, and mitochondrial dysfunction. Mitochondrial DNA abnormalities can include depletion, deletion, and point mutations (Taanman et al., 2009). Genetic Heterogeneity of Autosomal Recessive Mitochondrial DNA Depletion Syndromes Autosomal recessive mitochondrial DNA depletion syndromes are clinically and genetically heterogeneous. See also MTDPS2 (609560), caused by mutation in the TK2 gene (188250); MTDPS3 (251880), caused by mutation in the DGUOK gene (601465); MTDPS4A (203700) and MTDPS4B (613662), both caused by mutation in the POLG gene (174763); MTDPS5 (612073), caused by mutation in the SUCLA2 gene (603921); MTDPS6 (256810), caused by mutation in the MPV17 gene (137960); MTDPS7 (271245), caused by mutation in the C10ORF2 gene (606075); MTDPS8A (612075) and MTDPS8B (see 612075), both caused by mutation in the RRM2B gene (604712); MTDPS9 (245400), caused by mutation in the SUCLG1 gene (611224); MTDPS10 (212350), caused by mutation in the AGK gene (610345); MTDPS11 (615084), caused by mutation in the MGME1 gene (615076); MTDPS12 (615418), caused by mutation in the SLC25A4 gene (103220); and MTDPS13 (615471), caused by mutation in the FBXL4 gene (605654) on chromosome 6q16.  http://www.omim.org/entry/603041
From GHR
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is a condition that affects several parts of the body, particularly the digestive system and nervous system. The major features of MNGIE disease can appear anytime from infancy to adulthood, but signs and symptoms most often begin by age 20. The medical problems associated with this disorder worsen with time. Abnormalities of the digestive system are among the most common and severe features of MNGIE disease. Almost all affected people have a condition known as gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. The resulting digestive problems include feelings of fullness (satiety) after eating only a small amount, trouble swallowing (dysphagia), nausea and vomiting after eating, episodes of abdominal pain, diarrhea, and intestinal blockage. These gastrointestinal problems lead to extreme weight loss and reduced muscle mass (cachexia). MNGIE disease is also characterized by abnormalities of the nervous system, although these tend to be milder than the gastrointestinal problems. Affected individuals experience tingling, numbness, and weakness in their limbs (peripheral neuropathy), particularly in the hands and feet. Additional neurological signs and symptoms can include droopy eyelids (ptosis), weakness of the muscles that control eye movement (ophthalmoplegia), and hearing loss. Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter, is a hallmark of MNGIE disease. These changes in the brain can be seen with magnetic resonance imaging (MRI), though they usually do not cause symptoms in people with this disorder.  http://ghr.nlm.nih.gov/condition/mitochondrial-neurogastrointestinal-encephalopathy-disease

Clinical features

Cachexia
MedGen UID:
505610
Concept ID:
CN003827
Finding
Severe weight loss, wasting of muscle, loss of appetite, and general debility related to a chronic disease.
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Progressive external ophthalmoplegia
MedGen UID:
504513
Concept ID:
CN000553
Finding
Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Distal sensory impairment
MedGen UID:
373064
Concept ID:
C1836340
Finding
Leukoencephalopathy
MedGen UID:
505209
Concept ID:
CN002135
Finding
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
Hypointensity of cerebral white matter on MRI
MedGen UID:
776516
Concept ID:
CN006201
Finding
A darker than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
Gastrointestinal dysmotility
MedGen UID:
324638
Concept ID:
C1836923
Finding
Constipation
MedGen UID:
368096
Concept ID:
C1963087
Finding
Malabsorption
MedGen UID:
368423
Concept ID:
C1963165
Finding
Vomiting
MedGen UID:
776588
Concept ID:
C2712332
Finding
Abdominal pain
MedGen UID:
505060
Concept ID:
CN001834
Finding
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Intermittent diarrhea
MedGen UID:
505172
Concept ID:
CN002045
Finding
Gastroparesis
MedGen UID:
505277
Concept ID:
CN002340
Finding
Decreased strength of the Muscle layer of stomach, which leads to a decreased ability to empty the contents of the stomach despite the absence of obstruction.
Malnutrition
MedGen UID:
505624
Concept ID:
CN003893
Finding
Lactic acidosis
MedGen UID:
344523
Concept ID:
C1855560
Finding
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Ragged-red muscle fibers
MedGen UID:
477048
Concept ID:
C3275417
Finding
Multiple mitochondrial DNA deletions
MedGen UID:
479006
Concept ID:
C3277376
Finding
Progressive external ophthalmoplegia
MedGen UID:
504513
Concept ID:
CN000553
Finding
Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades.
Gastroparesis
MedGen UID:
505277
Concept ID:
CN002340
Finding
Decreased strength of the Muscle layer of stomach, which leads to a decreased ability to empty the contents of the stomach despite the absence of obstruction.
Subsarcolemmal accumulations of abnormally shaped mitochondria
MedGen UID:
505556
Concept ID:
CN003202
Finding
An abnormally increased number of mitochondria in the cytoplasma adjacent to the sarcolemma (muscle cell membrane), whereby the mitochondria also possess an abnormal morphology.
Decreased activity of cytochrome C oxidase in muscle tissue
MedGen UID:
505573
Concept ID:
CN003334
Finding
An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue.
Distal amyotrophy
MedGen UID:
505575
Concept ID:
CN003339
Finding
Muscular atrophy affecting muscles in the distal portions of the extremities.
Mitochondrial myopathy
MedGen UID:
505582
Concept ID:
CN003376
Finding
A type of myopathy associated with mitochondrial disease and characterized by findings on biopsy such as ragged red muscle fibers.

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