Phenotypes associated with the disease progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (OMIM:617070):
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 2/6. (PMID:23043144)
- Peripheral axonal neuropathy (HP:0003477): An abnormality characterized by disruption of the normal functioning of peripheral axons. Evidence: PCS. (PMID:23043144)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. (PMID:23043144)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 3/6. (PMID:23043144)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. (PMID:23043144)
- 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: 5/6. (PMID:23043144)
- Middle age onset (HP:0003596): A type of adult onset with onset of symptoms at the age of 40 to 60 years. Evidence: PCS. Frequency: 4/6. (PMID:23043144)
- Rhabdomyolysis (HP:0003201): Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream. Evidence: PCS. Frequency: 1/6. (PMID:23043144)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 1/2. (PMID:23043144)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: PCS. (PMID:23043144)
- Late onset (HP:0003584): A type of adult onset with onset of symptoms after the age of 60 years. Evidence: PCS. Frequency: 1/6. (PMID:23043144)
- Increased circulating lactate concentration (HP:0002151): Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35). Evidence: PCS. Frequency: 1/6. (PMID:23043144)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: PCS. (PMID:23043144)
- Dysphonia (HP:0001618): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: PCS. Frequency: 2/6. (PMID:23043144)
- 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: 1/6. (PMID:23043144)
- 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: 1/6. (PMID:23043144)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/6. (PMID:23043144)
- 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: 2/6. (PMID:23043144)
- 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:23043144)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: PCS. (PMID:23043144)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 6/6. (PMID:23043144)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 6/6. (PMID:23043144)