- 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:23462291)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 2/2. (PMID:23462291)
- 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: IEA. (OMIM:615330)
- 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: IEA. Frequency: Very rare (HP:0040284). (OMIM:615330)
- Elevated brain choline level by MRS (HP:0012706): An increase in the level of choline-containing compounds in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: PCS. Frequency: 1/1. (PMID:23462291)
- 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: PCS. Frequency: 2/2. (PMID:23462291)
- Severe muscular hypotonia (HP:0006829): A severe degree of muscular hypotonia characterized by markedly reduced muscle tone. Evidence: TAS. (OMIM:615330)
- Elevated lactate:pyruvate ratio (HP:0032653): An abnormal increase in the molar ratio of lactate to pyruvate in the blood circulation. Evidence: PCS. Frequency: 1/1. (PMID:23462291)
- Diminished alpha-ketoglutarate dehydrogenase activity in cultured fibroblasts (HP:6000830): Concentration or activity of the alpha-ketoglutarate dehydrogenase complex as measured in cultured fibroblasts is below the limits of normal. This enzyme is a multienzyme complex consisting of 3 protein subunits, oxoglutarate dehydrogenase, also known as alpha-ketoglutarate dehydrogenase or E1k (EC 1.2.4.2.), dihydrolipoyl succinyltransferase (DLST, or E2k; 126063), and dihydrolipoyl dehydrogenase (DLD, or E3; 238331). The complex catalyzes a key reaction in the Krebs tricarboxylic acid cycle. Evidence: TAS. (OMIM:615330)
- Beta-aminoisobutyric aciduria (HP:0032480): An increased amount of beta-aminoisobutyric acid in the urine. Beta-aminoisobutyric acid is a non-protein amino acid originating from the catabolism of thymine and valine. Evidence: PCS. Frequency: 1/1. (PMID:23462291)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: IEA. (OMIM:615330)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:615330)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: IEA. (OMIM:615330)
- 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: 2/2. (PMID:23462291)
- 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: IEA. (OMIM:615330)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/2. (PMID:23462291)
- 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: 1/2. (PMID:23462291)
- Wide intermamillary distance (HP:0006610): A larger than usual distance between the left and right nipple. Evidence: PCS. Frequency: 1/2. (PMID:23462291)
- Leukodystrophy (HP:0002415): Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies. Evidence: PCS. (PMID:23462291)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/2. (PMID:23462291)
- Metabolic acidosis (HP:0001942): Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause. Evidence: PCS. (PMID:23462291)
- 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:23462291)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/1. (PMID:23462291)
- Generalized muscle weakness (HP:0003324): Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature. Evidence: PCS. Frequency: 1/2. (PMID:23462291)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 2/2. (PMID:23462291)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 2/2. (PMID:23462291)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: IEA. (OMIM:615330)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: IEA. (OMIM:615330)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 1/1. (PMID:23462291)
- 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: 2/2. (PMID:23462291)
- Hyperglycinemia (HP:0002154): An elevated concentration of glycine in the blood. Evidence: PCS. Frequency: 1/1. (PMID:23462291)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 1/1. (PMID:23462291)
- 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:23462291)
- Respiratory insufficiency (HP:0002093). Evidence: IEA. (OMIM:615330)
- Increased CSF glycine concentration (HP:0500230): Abnormally increased levels of glycine in cerebrospinal fluid. Evidence: PCS. Frequency: 2/2. (PMID:23462291)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: PCS. Frequency: 2/2. (PMID:23462291)
- 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:23462291)
- Recurrent fever (HP:0001954): Periodic (episodic or recurrent) bouts of fever. Evidence: IEA. (OMIM:615330)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: IEA. (OMIM:615330)
- 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: IEA. (OMIM:615330)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/2. (PMID:23462291)
- Polymicrogyria (HP:0002126): Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds). Evidence: PCS. Frequency: 1/1. (PMID:23462291)
These phenotypes are associated with the disease multiple mitochondrial dysfunctions syndrome 3 (OMIM:615330).