Phenotypes associated with the disease mitochondrial DNA depletion syndrome 4b (OMIM:613662):
- 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:613662)
- Sensory ataxic neuropathy (HP:0003434). Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:613662)
- 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: 2/2. (PMID:12825077)
- Malabsorption (HP:0002024): Impaired ability to absorb one or more nutrients from the intestine. Evidence: TAS. (OMIM:613662)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:613662)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: TAS. (OMIM:613662)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: TAS. (OMIM:613662)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: TAS. (OMIM:613662)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:613662)
- Abdominal distention (HP:0003270): Distention of the abdomen. Evidence: TAS. (OMIM:613662)
- Depletion of mitochondrial DNA in muscle tissue (HP:0009141). Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- Weight loss (HP:0001824): Reduction of total body weight. Evidence: TAS. (OMIM:613662)
- 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: TAS. (OMIM:613662)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. (OMIM:613662)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- Generalized muscle weakness (HP:0003324): Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature. Evidence: TAS. (OMIM:613662)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- 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: PCS. Frequency: 2/2. (PMID:12825077)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:613662)
- Malnutrition (HP:0004395): A deficiency in the intake of energy and nutrients. Evidence: TAS. (OMIM:613662)
- Decreased activity of mitochondrial complex I (HP:0011923): A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- 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:12825077)
- Decreased activity of mitochondrial complex IV (HP:0008347): A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/2. (PMID:12825077)
- 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: PCS. (PMID:12825077)
- 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:613662)
- 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: TAS. (OMIM:613662)
- Abnormal cerebral white matter morphology (HP:0002500): An abnormality of the cerebral white matter. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:613662)
- Cachexia (HP:0004326): Severe weight loss, wasting of muscle, loss of appetite, and general debility related to a chronic disease. Evidence: PCS. Frequency: 2/2. (PMID:12825077)