- 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: IEA. (OMIM:614388)
- 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: TAS. (OMIM:614388)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- 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: TAS. (OMIM:614388)
- 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. Frequency: Occasional (HP:0040283). (OMIM:614388)
- 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: 11/11. (OMIM:614388;PMID:26992161)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:614388)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Self-biting (HP:0012169): Habitual biting of one's own body. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. (OMIM:614388)
- Broad hallux (HP:0010055): Visible increase in width of the hallux without an increase in the dorso-ventral dimension. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Pain insensitivity (HP:0007021): Inability to perceive painful stimuli. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Oculomotor apraxia (HP:0000657): Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancelation of the vestibulo-ocular reflex. Evidence: TAS. (OMIM:614388)
- Restlessness (HP:0000711): A state of unease is characterized by diffuse motor activity or motion, which is subject to limited control, nonproductive, or disorganized behavior. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: TAS. (OMIM:614388)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 2/2. (PMID:26992161;PMID:17460227)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. (OMIM:614388)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Status epilepticus (HP:0002133): Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614388)
- 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: 1/1. (PMID:17460227)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- 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: 1/1. (PMID:26992161)
- 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: 2/2. (PMID:26992161;PMID:17460227)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Broad thumb (HP:0011304): Increased thumb width without increased dorso-ventral dimension. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Elevated circulating hexacosanoic acid concentration (HP:0034298): The concentration of hexacosanoic acid (a C26 straight-chain saturated fatty acid) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: TAS. (OMIM:614388)
- 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: TAS. (OMIM:614388)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Epileptic encephalopathy (HP:0200134): A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614388)
- 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: TAS. (OMIM:614388)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Athetosis (HP:0002305): A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
- Autosomal dominant inheritance (HP:0000006): 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: PCS. (PMID:17460227)
- Horizontal nystagmus (HP:0000666): Nystagmus consisting of horizontal to-and-fro eye movements. Evidence: PCS. Frequency: 1/1. (PMID:17460227)
- Neonatal respiratory distress (HP:0002643): Respiratory difficulty as newborn. Evidence: PCS. Frequency: 1/1. (PMID:26992161)
These phenotypes are associated with the disease encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (OMIM:614388).