- 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: PCS. Frequency: 4/4. (PMID:21944046)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 11/14. (PMID:22077971;PMID:21944046)
- Increased urine alpha-ketoglutarate concentration (HP:0012402): A greater than normal concentration of 2-oxoglutaric acid in the urine. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 17/21. (PMID:22077971;PMID:21944046;PMID:24462778)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Decreased activity of mitochondrial respiratory chain (HP:0008972): Decreased activity of the mitochondrial respiratory chain. Evidence: PCS. Frequency: 3/3. (PMID:21944046)
- Alpha-aminoadipic aciduria (HP:0410309): The concentration of alpha-aminoadipic acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 10/10. (PMID:22077971)
- 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: 4/4. (PMID:21944046)
- Lacticaciduria (HP:0003648): An increased concentration of lactic acid in the urine. Evidence: PCS. Frequency: 1/1. (PMID:21944046)
- Decreased activity of mitochondrial complex II (HP:0008314): A reduction in the activity of the mitochondrial respiratory chain complex II, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. Frequency: 3/4. (PMID:21944046)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 1/4. (PMID:21944046)
- Hyperglycinuria (HP:0003108): An increased concentration of glycine in the urine. Evidence: PCS. Frequency: 8/8. (PMID:22077971;PMID:24462778)
- Episodic metabolic acidosis (HP:0004911): Repeated transient episodes of metabolic acidosis, that is, of the buildup of acid or depletion of base due to accumulation of metabolic acids. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- 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: 4/4. (PMID:21944046)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 3/4. (PMID:21944046)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Elevated circulating 2-hydroxybutyric acid concentration (HP:0033418): Elevation of the 2-hydroxybutyric acid concentration in the blood above the normal range. Evidence: PCS. Frequency: 1/1. (PMID:21944046)
- Facial paralysis (HP:0007209): Complete loss of ability to move facial muscles innervated by the facial nerve (i.e., the seventh cranial nerve). Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 4/10. (PMID:22077971)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 4/4. (PMID:21944046;PMID:24462778)
- Hyperglycinemia (HP:0002154): An elevated concentration of glycine in the blood. Evidence: PCS. Frequency: 10/12. (PMID:22077971;PMID:21944046;PMID:24462778)
- 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: PCS. Frequency: 1/1. (PMID:24462778)
- 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: 4/11. (PMID:22077971;PMID:21944046)
- 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: 11/11. (PMID:22077971;PMID:24462778)
- Spastic tetraparesis (HP:0001285): Spastic weakness affecting all four limbs. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 4/4. (PMID:22077971)
- Pulmonary arterial hypertension (HP:0002092): Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position. Evidence: PCS. Frequency: 7/10. (PMID:22077971)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 4/4. (PMID:21944046)
- Abnormality of extrapyramidal motor function (HP:0002071): A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless). Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Increased CSF glycine concentration (HP:0500230): Abnormally increased levels of glycine in cerebrospinal fluid. Evidence: PCS. Frequency: 8/8. (PMID:22077971;PMID:21944046)
- Motor regression (HP:0033044): Loss of previously achieved motor skills, as manifested by loss of developmental motor milestones. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- 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:21944046)
- Neonatal death (HP:0003811): Death within the first 28 days of life. Evidence: PCS. Frequency: 3/4. (PMID:21944046)
- Focal-onset seizure (HP:0007359): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 1/1. (PMID:24462778)
These phenotypes are associated with the disease multiple mitochondrial dysfunctions syndrome 1 (OMIM:605711).