Phenotypes associated with the disease D-2-hydroxyglutaric aciduria 1 (OMIM:600721):
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 2/2. (PMID:15609246)
- Hypsarrhythmia (HP:0002521): Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG). Evidence: PCS. Frequency: 1/2. (PMID:15609246)
- Delayed CNS myelination (HP:0002188): Delayed myelination in the central nervous system. Evidence: IEA. (OMIM:600721)
- 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: IEA. (OMIM:600721)
- 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: 1/2. (PMID:15609246)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/2. (PMID:15609246)
- Glutaric aciduria (HP:0003150): The concentration of glutaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: IEA. (OMIM:600721)
- 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: 1/2. (PMID:15609246)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 1/2. (PMID:15609246)
- 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: PCS. Frequency: 1/2. (PMID:15609246)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 1/2. (PMID:15609246)
- Subependymal cysts (HP:0002416): Cerebral cysts, usually located in the wall of the caudate nucleus or in the caudothalamic groove. They are found in up to 5.2% of all neonates, using transfontanellar ultrasound in the first days of life. Evidence: IEA. (OMIM:600721)
- Infantile encephalopathy (HP:0007105): Encephalopathy with onset in the infantile period. Evidence: IEA. (OMIM:600721)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: IEA. (OMIM:600721)
- 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: IEA. (OMIM:600721)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: IEA. (OMIM:600721)
- Inspiratory stridor (HP:0005348): Inspiratory stridor is a high pitched sound upon inspiration that is generally related to laryngeal abnormalities. Evidence: IEA. (OMIM:600721)
- Lateral ventricle dilatation (HP:0006956). Evidence: IEA. (OMIM:600721)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 1/2. (PMID:15609246)
- 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: PCS. Frequency: 20/20. (PMID:20020533;OMIM:600721)
- 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: 2/2. (PMID:15609246)
- D-2-hydroxyglutaric aciduria (HP:0012321): An increased concentration of 2-hydroxyglutaric acid in the urine. Evidence: PCS. Frequency: 2/2. (PMID:15609246)
- Multifocal cerebral white matter abnormalities (HP:0007052). Evidence: IEA. (OMIM:600721)
- Tonic seizure (HP:0032792): A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening. Evidence: PCS. Frequency: 1/2. (PMID:15609246)
- 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:15609246)
- 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: IEA. (OMIM:600721)
- Aortic regurgitation (HP:0001659): An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle. Evidence: IEA. (OMIM:600721)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: IEA. (OMIM:600721)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: IEA. (OMIM:600721)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/2. (PMID:15609246)