- 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: 32/53. (PMID:32777384)
- Acute encephalopathy (HP:0006846). Evidence: PCS. Frequency: 3/7. (PMID:27672653)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 5/7. (PMID:27672653)
- Elevated circulating glutaric acid concentration (HP:0003530): An increased concentration of glutaric acid in the blood. Evidence: IEA. (OMIM:231670)
- 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: 41/60. (PMID:27672653;OMIM:231670)
- 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: 21/60. (PMID:32777384;PMID:27672653)
- 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: TAS. (OMIM:231670)
- 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: IEA. (OMIM:231670)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 44/59. (PMID:32777384;PMID:27672653)
- Hyperketonemia (HP:0410175): An increase in the level of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the blood. Evidence: IEA. (OMIM:231670)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: IEA. (OMIM:231670)
- Glutaric aciduria (HP:0003150): The concentration of glutaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 54/60. (PMID:32777384;PMID:27672653)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:231670)
- Elevated urine 3-hydroxyglutaric level (HP:0034656): The concentration of 3-hydroxyglutaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 7/7. (PMID:27672653)
- Ketonuria (HP:0002919): High levels of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the urine. Ketone bodies are insignificant in the blood and urine of normal individuals in the postprandial or overnight-fasted state. Evidence: IEA. (OMIM:231670)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:231670)
- 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: 3/7. (PMID:27672653)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 11/52. (PMID:32777384)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: IEA. (OMIM:231670)
- Hydrocephalus (HP:0000238): Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation. Evidence: PCS. Frequency: 9/59. (PMID:32777384;PMID:27672653)
- Subdural hemorrhage (HP:0100309): Hemorrhage occurring between the dura mater and the arachnoid mater. Evidence: PCS. Frequency: 6/7. (PMID:27672653)
- Ketosis (HP:0001946): Presence of elevated levels of ketone bodies in the body. Evidence: IEA. (OMIM:231670)
- Symmetrical progressive peripheral demyelination (HP:0006873): A symmetric and progressive loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system. Evidence: IEA. (OMIM:231670)
- Infantile encephalopathy (HP:0007105): Encephalopathy with onset in the infantile period. Evidence: IEA. (OMIM:231670)
- 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: PCS. Frequency: 40/60. (PMID:32777384;PMID:27672653)
- Metabolic acidosis (HP:0001942): Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause. Evidence: IEA. (OMIM:231670)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/52. (PMID:32777384)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: IEA. (OMIM:231670)
- Spastic diplegia (HP:0001264): Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis. Evidence: IEA. (OMIM:231670)
- Lateral ventricle dilatation (HP:0006956). Evidence: IEA. (OMIM:231670)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 3/52. (PMID:32777384)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 1/7. (PMID:27672653)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. Frequency: 15/52. (PMID:32777384)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 5/7. (PMID:27672653)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 2/7. (PMID:27672653)
- Choreoathetosis (HP:0001266): Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements). Evidence: IEA. (OMIM:231670)
- 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:32777384)
- Reduced peroxisomal glutaryl-CoA oxidase activity (HP:0034688): Diminished enzyme activity of peroxisomal glutaryl-CoA oxidase, an enzyme that metabolizes glutaryl-CoA (a metabolite of L-lysine, L-hydroxy-lysine and L-tryptophan) by dehydrogenation to glutaconyl-CoA directly followed by decarboxylation of this to crotonyl-CoA. Evidence: PCS. Frequency: 181/181. (PMID:16641220)
- Enlarged sylvian cistern (HP:0100952): An increase in size of the subarachnoid space associated with the lateral cerebral sulcus (Sylvian fissure). Evidence: PCS. Frequency: 6/7. (PMID:27672653)
- Elevated circulating glutarylcarnitine concentration (HP:0033442): Concentration of glutarylcarnitine in the blood circulation above the upper limit of normal. Evidence: PCS. Frequency: 4/4. (PMID:27672653)
- 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: IEA. (OMIM:231670)
These phenotypes are associated with the disease glutaryl-CoA dehydrogenase deficiency (OMIM:231670).