- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. (PMID:26912632)
- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: TAS. (OMIM:615838)
- 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: PCS. (PMID:26912632)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: PCS. Frequency: 0/7. (PMID:26912632)
- Elevated brain lactate level by MRS (HP:0012707): An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 3/4. (PMID:26912632)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- 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: PCS. Frequency: 2/7. (PMID:26912632)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/6. (PMID:26912632)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Thin corpus callosum (HP:0033725): An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration). Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Abnormal circulating creatine kinase activity (HP:0040081): Any deviation from the normal activity of creatine kinase in the blood circulation. Evidence: PCS. Frequency: 0/4. (PMID:26912632)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. (PMID:26912632)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 3/7. (PMID:26912632)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 2/7. (PMID:24014394;PMID:26912632)
- Abnormal periventricular white matter morphology (HP:0002518): A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles. Evidence: PCS. Frequency: 7/7. (PMID:26912632)
- Atrophy/Degeneration affecting the brainstem (HP:0007366). Evidence: PCS. Frequency: 0/7. (PMID:26912632)
- Respiratory failure (HP:0002878): A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 4/6. (PMID:26912632)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 6/6. (PMID:26912632)
- 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: 7/7. (PMID:26912632)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 3/7. (PMID:26912632)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 2/7. (PMID:26912632)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 3/7. (PMID:26912632)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 2/7. (PMID:26912632)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 3/6. (PMID:26912632)
- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: PCS. Frequency: 6/6. (PMID:26912632)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 6/8. (PMID:24014394;PMID:26912632)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 6/6. (PMID:26912632)
- 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: 3/6. (PMID:26912632)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 3/7. (PMID:26912632)
- 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: PCS. Frequency: 7/7. (PMID:26912632)
- 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: 1/1. (PMID:24014394)
- Spastic tetraparesis (HP:0001285): Spastic weakness affecting all four limbs. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 2/2. (PMID:26912632)
- Elevated circulating acylcarnitine concentration (HP:0045045): Concentration of acylcarnitine in the blood circulation above the upper limit of normal. Evidence: PCS. Frequency: 0/3. (PMID:26912632)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- 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: 2/7. (PMID:26912632)
- 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:24014394)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: PCS. Frequency: 5/7. (PMID:26912632)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: PCS. Frequency: 5/7. (PMID:26912632)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: PCS. Frequency: 6/6. (PMID:26912632)
- Tachypnea (HP:0002789): Very rapid breathing. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- Coma (HP:0001259): The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli. Evidence: PCS. Frequency: 1/1. (PMID:24014394)
- External ophthalmoplegia (HP:0000544): Paralysis of the external ocular muscles. Evidence: PCS. Frequency: 3/7. (PMID:26912632)
- Rapidly progressive (HP:0003678): Applies to a disease manifestation that quickly increases in scope or severity over the course of time. Evidence: TAS. (OMIM:615838)
These phenotypes are associated with the disease mitochondrial complex III deficiency nuclear type 8 (OMIM:615838).