Phenotypes associated with the disease mitochondrial DNA depletion syndrome 1 (OMIM:603041):
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: TAS. (OMIM:603041)
- Malabsorption (HP:0002024): Impaired ability to absorb one or more nutrients from the intestine. Evidence: IEA. (OMIM:603041)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: PCS. Frequency: 11/11. (PMID:14757860;OMIM:603041)
- Early satiety (HP:0033842): The condition of being unable to eat a full meal because of a feeling of fullness (satiety), or or feeling very full after eating only a small amount of food. Evidence: PCS. Frequency: 14/15. (PMID:10852545)
- Distal sensory impairment (HP:0002936): An abnormal reduction in sensation in the distal portions of the extremities. Evidence: IEA. (OMIM:603041)
- Gastrointestinal dysmotility (HP:0002579): Abnormal intestinal contractions, such as spasms and intestinal paralysis, related to the loss of the ability of the gut to coordinate muscular activity because of endogenous or exogenous causes. Evidence: IEA. (OMIM:603041)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. (OMIM:603041)
- Subsarcolemmal accumulations of abnormally shaped mitochondria (HP:0003548): An abnormally increased number of mitochondria in the cytoplasma adjacent to the sarcolemma (muscle cell membrane), whereby the mitochondria also possess an abnormal morphology. Evidence: IEA. (OMIM:603041)
- Ophthalmoparesis (HP:0000597): Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement. Evidence: PCS. Frequency: 35/35. (PMID:10852545)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 1/35. (PMID:10852545)
- Gastroparesis (HP:0002578): 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. Evidence: PCS. Frequency: 4/7. (PMID:10852545)
- Ragged-red muscle fibers (HP:0003200): An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm. Evidence: IEA. (OMIM:603041)
- Diplopia (HP:0000651): Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision. Evidence: PCS. Frequency: 1/1. (PMID:14757860)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: IEA. (OMIM:603041)
- Hyperactive bowel sounds (HP:0030143): Abnormally increased gurgling/rumbling sounds made by the movement of fluid and gas in the intestines. Evidence: PCS. Frequency: 24/25. (PMID:10852545)
- Allodynia (HP:0012533): Pain due to a stimulus that does not normally provoke pain. Evidence: PCS. Frequency: 1/1. (PMID:14757860)
- Elevated circulating thymidine concentration (HP:0034276): Concentration of thymidine in the blood circulation above the normal range. Evidence: PCS. Frequency: 1/1. (PMID:14757860)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: PCS. Frequency: 14/31. (PMID:10852545)
- Dementia (HP:0000726): A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. Evidence: PCS. Frequency: 0/35. (PMID:10852545)
- Death in early adulthood (HP:0100613): Death between the age of 16 and 40 years. Evidence: TAS. (OMIM:603041)
- Elevated circulating deoxyuridine concentration (HP:0034277): Concentration of 2-deoxyuridine in the blood circulation is above the normal range. Evidence: PCS. Frequency: 1/1. (PMID:14757860)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:9924029)
- Slender build (HP:0001533): Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones. Evidence: IEA. (OMIM:603041)
- Abdominal pain (HP:0002027): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen. Evidence: PCS. Frequency: 17/18. (PMID:10852545)
- Cachexia (HP:0004326): Severe weight loss, wasting of muscle, loss of appetite, and general debility related to a chronic disease. Evidence: TAS. (OMIM:603041)
- Hypoesthesia (HP:0033748): Decreased ability to perceive touch. Evidence: PCS. Frequency: 1/1. (PMID:14757860)
- Intestinal pseudo-obstruction (HP:0004389): A functional rather than mechanical obstruction of the intestines, associated with manifestations that resemble those caused by an intestinal obstruction, including distension, abdominal pain, nausea, vomiting, constipation or diarrhea, in an individual in whom a mechanical blockage has been excluded. Evidence: PCS. Frequency: 11/17. (PMID:10852545)
- Reduced tissue thymidine phosphorylase activity (HP:6000570): Activity of thymidine phosphorylase (EC 2.4.2.4) in the tissues below the lower limit of normal. The activity can be measured in multiple tissues including leukocytes. Evidence: PCS. Frequency: 16/16. (PMID:10852545)
- Distal amyotrophy (HP:0003693): Muscular atrophy affecting muscles in the distal portions of the extremities. Evidence: IEA. (OMIM:603041)
- Intestinal perforation (HP:0031368): A hole (perforation) in the wall of the intestine. Evidence: IEA. (OMIM:603041)
- Sensorimotor neuropathy (HP:0007141). Evidence: PCS. Frequency: 1/1. (PMID:14757860)
- Hypointensity of cerebral white matter on MRI (HP:0007103): A darker than expected signal on magnetic resonance imaging emanating from the cerebral white matter. Evidence: IEA. (OMIM:603041)
- Weight loss (HP:0001824): Reduction of total body weight. Evidence: PCS. Frequency: 20/20. (PMID:10852545;PMID:14757860)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: IEA. (OMIM:603041)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: IEA. (OMIM:603041)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 0/1. (PMID:14757860)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: PCS. Frequency: 27/29. (PMID:10852545)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 12/28. (PMID:10852545)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/1. (PMID:14757860)
- Intermittent diarrhea (HP:0002254): Repeated episodes of diarrhea separated by periods without diarrhea. Evidence: IEA. (OMIM:603041)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 24/32. (PMID:10852545;PMID:14757860)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: PCS. Frequency: 11/11. (PMID:14757860;OMIM:603041)
- Colonic diverticula (HP:0002253): The presence of multiple diverticula of the colon. Evidence: PCS. Frequency: 16/24. (PMID:10852545)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 27/33. (PMID:10852545)
- Malnutrition (HP:0004395): A deficiency in the intake of energy and nutrients. Evidence: IEA. (OMIM:603041)
- Ptosis (HP:0000508): 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). Evidence: PCS. Frequency: 35/35. (PMID:10852545;PMID:14757860)
- Abdominal cramps (HP:0032155): A type of abdominal pain characterized by a feeling of contractions and typically fluctuating in intensity. Evidence: PCS. Frequency: 25/28. (PMID:10852545)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: PCS. Frequency: 34/34. (PMID:10852545)
- Mitochondrial myopathy (HP:0003737): A type of myopathy associated with mitochondrial disease and characterized by findings on biopsy such as ragged red muscle fibers. Evidence: IEA. (OMIM:603041)
- Areflexia of lower limbs (HP:0002522): Inability to elicit tendon reflexes in the lower limbs. Evidence: PCS. Frequency: 1/1. (PMID:14757860)