- 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: TAS. (OMIM:615182)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:615182)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: TAS. (OMIM:615182)
- Stridor (HP:0010307): Stridor is a high pitched sound resulting from turbulent air flow in the upper airway. Evidence: TAS. (OMIM:615182)
- 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:615182)
- 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: 12/12. (PMID:23561848)
- Elevated CSF D-2-hydroxyglutaric acid concentration (HP:6000246): The concentration of D-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF) is above the upper limit of normal. Evidence: TAS. (OMIM:615182)
- 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: 11/11. (PMID:23561848)
- Severe muscular hypotonia (HP:0006829): A severe degree of muscular hypotonia characterized by markedly reduced muscle tone. Evidence: TAS. (OMIM:615182)
- 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: 10/10. (PMID:23561848)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:615182)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. (OMIM:615182)
- Dyspnea (HP:0002094): Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale. Evidence: TAS. (OMIM:615182)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. (OMIM:615182)
- Increased urine alpha-ketoglutarate concentration (HP:0012402): A greater than normal concentration of 2-oxoglutaric acid in the urine. Evidence: PCS. Frequency: 9/11. (PMID:23561848)
- Elevated CSF L-2-hydroxyglutaric acid concentration (HP:6000509): The concentration of L-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF) is above the upper limit of normal. Evidence: TAS. (OMIM:615182)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:615182)
- 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: TAS. (OMIM:615182)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: TAS. (OMIM:615182)
- L-2-hydroxyglutaric aciduria (HP:0040144): An increase in the level of L-2-hydroxyglutaric acid in the urine. Evidence: PCS. Frequency: 12/12. (PMID:23561848)
- 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:23561848)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. (OMIM:615182)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:615182)
- Increased urine succinate level (HP:0033092): The concentration of succinate in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 7/8. (PMID:23561848)
These phenotypes are associated with the disease D,L-2-hydroxyglutaric aciduria (OMIM:615182).