Phenotypes associated with the disease encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (OMIM:617668):
- 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: 3/3. (PMID:28757203)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- 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: 1/3. (PMID:28757203)
- 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:28757203)
- 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:28757203)
- Diminished alpha-ketoglutarate dehydrogenase activity in cultured fibroblasts (HP:6000830): Concentration or activity of the alpha-ketoglutarate dehydrogenase complex as measured in cultured fibroblasts is below the limits of normal. This enzyme is a multienzyme complex consisting of 3 protein subunits, oxoglutarate dehydrogenase, also known as alpha-ketoglutarate dehydrogenase or E1k (EC 1.2.4.2.), dihydrolipoyl succinyltransferase (DLST, or E2k; 126063), and dihydrolipoyl dehydrogenase (DLD, or E3; 238331). The complex catalyzes a key reaction in the Krebs tricarboxylic acid cycle. Evidence: TAS. (OMIM:617668)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 3/3. (PMID:28757203)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 2/3. (PMID:28757203)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 3/3. (PMID:28757203)
- 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: 2/3. (PMID:28757203)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 3/3. (PMID:28757203)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/1. (PMID:28757203)
- Periventricular cysts (HP:0007109). Evidence: PCS. Frequency: 2/3. (PMID:28757203)
- Lateral ventricle dilatation (HP:0006956). Evidence: PCS. Frequency: 2/3. (PMID:28757203)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/1. (PMID:28757203)
- Absent posterior alpha rhythm (HP:0031518): Lack of normal alpha rhythm in the EEG. Alpha rhythm has been defined as a rhythm at 8-13 Hz occurring during wakefulness over the posterior regions of the head, generally with higher voltage over the occipital areas. Amplitude is variable but is mostly below 50 microvolt in adults. It is best seen with eyes closed and under conditions of physical relaxation and relative mental inactivity. It is blocked or attenuated by attention, especially visual and mental effort. One should here note the difference between the terms alpha rhythm and alpha activity: Alpha activity refers to activity in the range of 8-13 Hz and alpha rhythm is the activity of 8-13 Hz with specific characteristics as defined above. Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- Increased circulating pyruvate concentration (HP:0003542): The concentration of pyruvate in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- 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:28757203)
- Hyperglycinemia (HP:0002154): An elevated concentration of glycine in the blood. Evidence: PCS. Frequency: 2/3. (PMID:28757203)
- 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: 3/3. (PMID:28757203)
- 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: 3/3. (PMID:28757203)
- Spastic tetraparesis (HP:0001285): Spastic weakness affecting all four limbs. Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: PCS. Frequency: 1/1. (PMID:28757203)
- Profound global developmental delay (HP:0012736): A profound delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 3/3. (PMID:28757203)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 1/3. (PMID:28757203)
- 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:28757203)
- Simplified gyral pattern (HP:0009879): An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly. Evidence: PCS. Frequency: 1/3. (PMID:28757203)