- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- 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: 2/3. (PMID:37133451)
- 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: 2/2. (PMID:37133451)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Cerebral edema (HP:0002181): Abnormal accumulation of fluid in the brain. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Severely reduced left ventricular ejection fraction (HP:0012666): A large reduction in the fraction of blood pumped from the left ventricle with each cardiac cycle. The normal range in adults is at over 50 percent, and a severe reduction is defined as less than 30 percent. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Abnormal basal ganglia MRI signal intensity (HP:0012751): A deviation from normal signal on magnetic resonance imaging (MRI) of the basal ganglia. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 2/3. (PMID:37133451)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- CNS demyelination (HP:0007305): A loss of myelin from nerve fibers in the central nervous system. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 2/3. (PMID:37133451)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- 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: 2/3. (PMID:37133451)
- Migraine (HP:0002076): Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- 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: 2/3. (PMID:37133451)
- 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: 1/3. (PMID:37133451)
- Ketotic hypoglycemia (HP:0012734): Low blood glucose is accompanied by elevated levels of ketone bodies in the body. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Cholelithiasis (HP:0001081): Hard, pebble-like deposits that form within the gallbladder. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- 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: 1/1. (PMID:37133451)
- Decreased activity of the pyruvate dehydrogenase complex (HP:0002928). Evidence: PCS. Frequency: 1/2. (PMID:37133451)
- Hypertrophic cardiomyopathy (HP:0001639): Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Retinal degeneration (HP:0000546): A nonspecific term denoting progressive loss of the retinal pigment epithelium (RPE) and/or neurosensory retinal cells. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Congestive heart failure (HP:0001635): The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- 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:37133451)
- 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: 2/2. (PMID:37133451)
- Apathy (HP:0000741): Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Attention deficit hyperactivity disorder (HP:0007018): Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient. Evidence: PCS. Frequency: 1/1. (PMID:37133451)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
- Dicarboxylic aciduria (HP:0003215): An increased concentration of dicarboxylic acid in the urine. Evidence: PCS. Frequency: 1/3. (PMID:37133451)
These phenotypes are associated with the disease combined oxidative phosphorylation deficiency 59 (OMIM:620646).