Phenotypes associated with the disease encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 (OMIM:617186):
- 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: 5/5. (PMID:27122014)
- 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: 1/6. (PMID:27616477)
- 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: PCS. Frequency: 3/12. (PMID:27616477)
- 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:27616477)
- Rigidity (HP:0002063): Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- 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: 7/12. (PMID:27616477)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 6/11. (PMID:27122014;PMID:27616477)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: PCS. Frequency: 4/6. (PMID:27616477)
- Myoclonic seizure (HP:0032794): A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- Cerebellar edema (HP:0030915): Swelling from fluid accumulation (serous fluid infiltration into the interstitial space) in the cerebellum. Evidence: PCS. Frequency: 8/12. (PMID:27616477)
- Cerebral edema (HP:0002181): Abnormal accumulation of fluid in the brain. Evidence: PCS. Frequency: 3/6. (PMID:27616477)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. (PMID:27616477)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 7/12. (PMID:27616477)
- 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: PCS. Frequency: 1/6. (PMID:27616477)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 5/6. (PMID:27616477)
- 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: 1/6. (PMID:27616477)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 3/6. (PMID:27616477)
- 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: Childhood onset (HP:0011463). (PMID:27122014)
- Cervical myelopathy (HP:0002318): A collection of pathologic conditions that result from progressive spinal cord dysfunction secondary to cord compression in the cervical spine. Evidence: PCS. Frequency: 2/6. (PMID:27616477)
- Abducens palsy (HP:0006897): Malfunction of the abducens nerve as manifested by impairment of the ability of the affected eye to be moved outward. Patients who develop abducens nerve palsy often present with binocular horizontal diplopia, which is a double vision when looking at objects side by side. There will be a notable weakness of the ipsilateral lateral rectus muscle leading to a deficit in of eye abduction on the affected side. Some patients may present with a constant head turning movement to maintain binocular fusion and to lessen the degree of diplopia. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- Vertical supranuclear gaze palsy (HP:0000511): A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- Skin erosion (HP:0200041): A discontinuity of the skin exhibiting incomplete loss of the epidermis, a lesion that is moist, circumscribed, and usually depressed. Evidence: PCS. (PMID:27616477)
- 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. (PMID:27616477)
- Torticollis (HP:0000473): Involuntary contractions of the neck musculature resulting in an abnormal posture of or abnormal movements of the head. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 6/11. (PMID:27122014;PMID:27616477)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: PCS. (PMID:27616477)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- 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:27616477)
- 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. (PMID:27616477)
- Tetraparesis (HP:0002273): Weakness of all four limbs. Evidence: PCS. Frequency: 2/6. (PMID:27616477)
- Myelopathy (HP:0002196): Myelopathy is an descriptive term, referring to pathology leading to a neurologic deficit related to the spinal cord. The clinical diagnosis of myelopathy requires a detailed history and physical examination to define the clinical syndrome. Neuroimaging is indicated in most instances of new-onset myelopathy. It is indicated also when the worsening of a myelopathy is unexplained. Evidence: PCS. Frequency: 3/3. (PMID:27616477)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 6/6. (PMID:27616477)
- Abnormal activity of mitochondrial respiratory chain (HP:0011922): An increased or decreased activity of the mitochondrial respiratory chain. Evidence: PCS. Frequency: 0/5. (PMID:27122014)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- Cerebral white matter atrophy (HP:0012762): The presence of atrophy (wasting) of the cerebral white matter. Evidence: PCS. Frequency: 1/5. (PMID:27616477)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: PCS. Frequency: 10/11. (PMID:27122014;PMID:27616477)
- 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:27122014)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 1/6. (PMID:27616477)
- Rapidly progressive (HP:0003678): Applies to a disease manifestation that quickly increases in scope or severity over the course of time. Evidence: PCS. (PMID:27122014)
- Coma (HP:0001259): The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli. Evidence: PCS. Frequency: 6/6. (PMID:27616477)
- Bradypnea (HP:0046507): Bradypnea is referring to breathing that is abnormally slow. Evidence: PCS. Frequency: 2/6. (PMID:27616477)