- 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: 2/5. (PMID:23022099)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: TAS. (OMIM:614922)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 5/5. (PMID:23022099)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. (OMIM:614922)
- Decreased liver function (HP:0001410): Reduced ability of the liver to perform its functions. Evidence: TAS. (OMIM:614922)
- Renal hypoplasia (HP:0000089): Hypoplasia of the kidney. Evidence: TAS. (OMIM:614922)
- 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: TAS. (OMIM:614922)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: TAS. (OMIM:614922)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: TAS. (OMIM:614922)
- Renal insufficiency (HP:0000083): A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism. Evidence: PCS. Frequency: 5/5. (PMID:23022099)
- Severe muscular hypotonia (HP:0006829): A severe degree of muscular hypotonia characterized by markedly reduced muscle tone. Evidence: TAS. (OMIM:614922)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614922)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 4/5. (PMID:23022099)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. (OMIM:614922)
- Renal tubular acidosis (HP:0001947): Acidosis owing to malfunction of the kidney tubules with accumulation of metabolic acids and hyperchloremia, potentially leading to complications including hypokalemia, hypercalcinuria, nephrolithiasis and nephrocalcinosis. Evidence: TAS. (OMIM:614922)
- Stillbirth (HP:0003826): Death of the fetus in utero after at least 22 weeks of gestation. Evidence: PCS. Frequency: 1/5. (PMID:23022099)
- Tongue fasciculations (HP:0001308): Fasciculations or fibrillation affecting the tongue muscle. Evidence: PCS. Frequency: 2/5. (PMID:23022099)
- 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: 5/5. Onset: Neonatal onset (HP:0003623). (PMID:23022099)
- CNS hypomyelination (HP:0003429): Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis. Evidence: TAS. (OMIM:614922)
- Pachygyria (HP:0001302): Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly. Evidence: TAS. (OMIM:614922)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 12/15. (PMID:23022099;OMIM:614922)
- 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:23022099)
- Renal dysplasia (HP:0000110): The presence of developmental dysplasia of the kidney. Evidence: TAS. (OMIM:614922)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 2/5. (PMID:23022099)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 2/5. (PMID:23022099)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: IEA. (OMIM:614922)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. (OMIM:614922)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. (OMIM:614922)
- 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: 4/4. (PMID:23022099)
- 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: TAS. (OMIM:614922)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/5. (PMID:23022099)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: TAS. (OMIM:614922)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: PCS. Frequency: 1/5. (PMID:23022099)
- Renal cyst (HP:0000107): A fluid filled sac in the kidney. Evidence: TAS. (OMIM:614922)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614922)
- 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:23022099)
- Cardiomyopathy (HP:0001638): A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614922)
- Neonatal death (HP:0003811): Death within the first 28 days of life. Evidence: PCS. Frequency: 1/5. (PMID:23022099)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614922)
These phenotypes are associated with the disease combined oxidative phosphorylation defect type 11 (OMIM:614922).