- Stroke (HP:0001297): Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain. Evidence: PCS. Frequency: 0/1. (PMID:39230499)
- 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. Frequency: 4/4. (PMID:39230499)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 0/4. (PMID:39230499)
- 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: PCS. Frequency: 0/1. (PMID:39230499)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. Frequency: 2/2. (PMID:39230499)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/4. (PMID:39230499)
- Increased endomysial connective tissue (HP:0100297): An increased volume of the endomysium, which is a connective tissue sheath that surrounds each muscle fiber. Together, bundles of muscle fibers form a fasciculus, surrounded by another layer of connective tissue called the perimysium. Evidence: PCS. Frequency: 2/4. (PMID:39230499)
- Chronic fatigue (HP:0012432): Subjective feeling of tiredness characterized by a lack of energy and motivation that persists for six months or longer. Evidence: PCS. Frequency: 4/4. (PMID:39230499)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: PCS. Frequency: 2/4. (PMID:39230499)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/4. (PMID:39230499)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Telangiectasia (HP:0001009): Telangiectasias refer to small dilated blood vessels located near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Telangiectasia are located especially on the tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips. Evidence: PCS. Frequency: 0/1. (PMID:39230499)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: PCS. Frequency: 2/2. (PMID:39230499)
- 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: PCS. Frequency: 0/4. (PMID:39230499)
- Ophthalmoparesis (HP:0000597): Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement. Evidence: PCS. Frequency: 1/3. (PMID:39230499)
- Bilateral ptosis (HP:0001488). Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Centrally nucleated skeletal muscle fibers (HP:0003687): An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells). Evidence: PCS. Frequency: 2/2. (PMID:39230499)
- 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: 4/4. (PMID:39230499)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: PCS. Frequency: 2/4. (PMID:39230499)
- Migraine (HP:0002076): Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. Evidence: PCS. Frequency: 1/3. (PMID:39230499)
- Decreased activity of mitochondrial complex III (HP:0011924): A reduction in the activity of the mitochondrial respiratory chain complex III, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/2. (PMID:39230499)
- Enlargement of parotid gland (HP:0011801): Increased size of the parotid gland. Evidence: PCS. Frequency: 1/4. (PMID:39230499)
- 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:39230499)
- Telangiectasia of the skin (HP:0100585): Presence of small, permanently dilated blood vessels near the surface of the skin, visible as small focal red lesions. Evidence: PCS. Frequency: 1/3. (PMID:39230499)
- Generalized limb muscle atrophy (HP:0009055): Generalized (unlocalized) atrophy affecting muscles of the limbs in both proximal and distal locations. Evidence: PCS. Frequency: 3/4. (PMID:39230499)
- Autistic behavior (HP:0000729): Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior. Evidence: PCS. Frequency: 0/3. (PMID:39230499)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- 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:39230499)
- 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: 1/1. (PMID:39230499)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Increased variability in muscle fiber diameter (HP:0003557): An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy. Evidence: PCS. Frequency: 4/4. (PMID:39230499)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/4. (PMID:39230499)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: PCS. Frequency: 4/4. (PMID:39230499)
- Decreased total CD4+ T cell proportion (HP:0032218): Abnormal decrease of helper CD3+CD4+ T cells, measured as percentage of total CD3+ T cells in the blood, compared to a reference range for a given sex and age-group. These are usually measured within the TCR alpha/beta positive population. Evidence: PCS. Frequency: 3/4. (PMID:39230499)
- Insomnia (HP:0100785): Persistent difficulty in starting or maintaining sleep, or waking up earlier than desired, despite having adequate opportunities and conditions for sleep. Evidence: PCS. Frequency: 1/4. (PMID:39230499)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 2/4. (PMID:39230499)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Anxiety (HP:0000739): Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. Evidence: PCS. Frequency: 1/4. (PMID:39230499)
- Mitochondrial respiratory chain defects (HP:0200125). Evidence: PCS. Frequency: 4/4. (PMID:39230499)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Headache (HP:0002315): Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve. Evidence: PCS. Frequency: 0/1. (PMID:39230499)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 3/4. (PMID:39230499)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 4/4. (PMID:39230499)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 4/4. (PMID:39230499)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/4. (PMID:39230499)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 0/3. (PMID:39230499)
- Asthma (HP:0002099): Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 2/4. (PMID:39230499)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 2/2. (PMID:39230499)
- 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: 3/3. (PMID:39230499)
- Abnormal total natural killer cell count (HP:0040089): Abnormal increase or decrease of total natural killer (NK) cells, commonly characterized as CD3-CD19- and CD16+ or CD56+ lymphocytes, in the blood, per microlitre, or altered NK cell phenotype, compared to a reference range for a given sex and age-group, measured ex vivo. Evidence: PCS. Frequency: 0/1. (PMID:39230499)
- 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: 1/4. (PMID:39230499)
- 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: 1/1. (PMID:39230499)
- Cardiomyopathy (HP:0001638): A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Evidence: PCS. Frequency: 1/4. (PMID:39230499)
- Impaired distal vibration sensation (HP:0006886): A decrease in the ability to perceive vibration in the distal portions of the limbs. Evidence: PCS. Frequency: 1/1. (PMID:39230499)
- Immunodeficiency (HP:0002721): Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance. Evidence: PCS. Frequency: 2/2. (PMID:39230499)
- Glucose intolerance (HP:0001952): Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM). Evidence: PCS. Frequency: 1/4. (PMID:39230499)
These phenotypes are associated with the disease mitochondrial dna depletion syndrome 21 (OMIM:621071).