- 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. Frequency: 2/2. (PMID:33169484)
- 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: 1/2. (PMID:33169484)
- Hepatic failure (HP:0001399). Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Abnormality of the coagulation cascade (HP:0003256): An abnormality of the coagulation cascade, which is comprised of the contact activation pathway (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway) as well as cofactors and regulators. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- 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: 1/1. (PMID:33169484)
- Elevated circulating dodecanoylcarnitine concentration (HP:0033444): Concentration of dodecanoylcarnitine (C12:0) in the blood circulation above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Elevated circulating tetradecanoylcarnitine concentration (HP:0033465): The concentration of tetradecanoylcarnitine in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Cerebral edema (HP:0002181): Abnormal accumulation of fluid in the brain. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Widened subarachnoid space (HP:0012704): An increase in size of the anatomic space between the arachnoid membrane and pia mater. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Increased urine alpha-ketoglutarate concentration (HP:0012402): A greater than normal concentration of 2-oxoglutaric acid in the urine. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Ketonuria (HP:0002919): High levels of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the urine. Ketone bodies are insignificant in the blood and urine of normal individuals in the postprandial or overnight-fasted state. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Setting-sun eye phenomenon (HP:0012470): An ophthalmologic sign in young children resulting from upward-gaze paresis. In this condition, the eyes appear driven downward, the sclera may be seen between the upper eyelid and the iris, and part of the lower pupil may be covered by the lower eyelid. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Fetal onset (HP:0011461): Onset prior to birth but after 8 weeks of embryonic development (corresponding to a gestational age of 10 weeks). Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 2/2. Onset: Neonatal onset (HP:0003623). (PMID:33169484)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: PCS. Frequency: 2/2. (PMID:33169484)
- Hyperprolinemia (HP:0008358): The concentration of proline in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:33169484)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 2/2. (PMID:33169484)
- 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: 2/2. (PMID:33169484)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- EEG abnormality (HP:0002353): Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp. Evidence: PCS. Frequency: 2/2. (PMID:33169484)
- Increased circulating pyruvate concentration (HP:0003542): The concentration of pyruvate in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:33169484)
- 3-hydroxydicarboxylic aciduria (HP:0008160): The concentration of 2-hydroxydicarboxylic acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- 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:33169484)
- 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: 1/2. (PMID:33169484)
- Left ventricular hypertrophy (HP:0001712): Enlargement or increased size of the heart left ventricle. Evidence: PCS. Frequency: 2/2. (PMID:33169484)
- 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:33169484)
- Ethylmalonic aciduria (HP:0003219): The concentration of ethylmalonic acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Hyperglutaminemia (HP:0003217): The concentration of glutamine in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Severe lactic acidosis (HP:0004900): A severe form of lactic acidemia. Evidence: PCS. Frequency: 2/2. (PMID:33169484)
- Congenital sensorineural hearing impairment (HP:0008527): A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
- Dicarboxylic aciduria (HP:0003215): An increased concentration of dicarboxylic acid in the urine. Evidence: PCS. Frequency: 1/2. (PMID:33169484)
These phenotypes are associated with the disease mitochondrial complex IV deficiency, nuclear type 22 (OMIM:619355).