- 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: 5/34. (PMID:28583327)
- Cardiac arrest (HP:0001695): An abrupt loss of heart function. Evidence: PCS. Frequency: 1/34. (PMID:28583327)
- Decreased circulating carnitine concentration (HP:0003234): Concentration of carnitine in the blood circulation below the lower limit of normal. Evidence: TAS. (OMIM:246450)
- Organic aciduria (HP:0001992): Excretion of non-amino organic acids in urine. Evidence: IEA. (OMIM:246450)
- Pallor (HP:0000980): Abnormally pale skin. Evidence: PCS. Frequency: 10/34. (PMID:28583327)
- 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: 17/34. (PMID:28583327)
- 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: 11/34. (PMID:28583327)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 13/34. (PMID:28583327)
- 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:246450)
- Increased level of 3-hydroxy-3-methylglutaric acid in urine (HP:0410051): The concentration of 3-hydroxy-3-methylglutaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. (PMID:23705938)
- Reduced HMG-CoA lyase activity in cultured fibroblasts (HP:6000216): Activity of 3-hydroxy-3-methylglutaryl coenzyme A lyase (HMG CoA lyase) below the lower limit of normal in cultured fibroblasts. Evidence: PCS. Frequency: 13/13. (PMID:28583327)
- Elevated serum anion gap (HP:0031962): An abnormally high value of the serum anion gap (the sum of serum chloride and bicarbonate concentrations subtracted from the serum sodium concentration). Evidence: PCS. Frequency: 9/10. (PMID:28583327)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 14/20. (PMID:28583327)
- 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: PCS. Frequency: 2/7. (PMID:28583327)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: IEA. (OMIM:246450)
- Elevated urinary 3-methylcrotonylglycine level (HP:0033596): An abnormally increased amount of 3-methylcrotonylglycine in the urine. Evidence: PCS. (PMID:28583327)
- Dehydration (HP:0001944). Evidence: PCS. Frequency: 3/34. (PMID:28583327)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 19/20. (PMID:28583327)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 25/28. (PMID:28583327)
- Fever (HP:0001945): Body temperature elevated above the normal range. Evidence: PCS. Frequency: 3/34. (PMID:28583327)
- 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: PCS. Frequency: 20/20. (PMID:28583327)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: PCS. Frequency: 3/34. (PMID:28583327)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 2/34. (PMID:28583327)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 14/20. (PMID:28583327)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/34. (PMID:28583327)
- EEG abnormality (HP:0002353): Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp. Evidence: IEA. (OMIM:246450)
- 3-Methylglutaric aciduria (HP:0003344): An abnormally increased level of 3-hydroxy-3-methylglutaric acid in the urine. Evidence: PCS. (PMID:28583327)
- Increased level of hippuric acid in urine (HP:0410066): An increase in the level of hippuric acid in the urine. Evidence: PCS. (PMID:22626821)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 17/34. (PMID:28583327)
- 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: 17/35. (PMID:28583327)
- 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: 7/12. (PMID:28583327)
- Excessive daytime somnolence (HP:0001262): A state of abnormally strong desire for sleep during the daytime. Evidence: IEA. (OMIM:246450)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: IEA. (OMIM:246450)
- Decreased prothrombin time (HP:0032198): Abnormally short time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT. Evidence: PCS. Frequency: 6/20. (PMID:28583327)
- 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:28583327)
- Drowsiness (HP:0002329): Abnormal feeling of sleepiness or difficulty staying awake. Evidence: PCS. Frequency: 13/34. (PMID:28583327)
- Apathy (HP:0000741): Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy. Evidence: PCS. Frequency: 13/34. (PMID:28583327)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: PCS. Frequency: 1/34. (PMID:28583327)
- Abnormal cerebral white matter morphology (HP:0002500): An abnormality of the cerebral white matter. Evidence: IEA. (OMIM:246450)
- 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: IEA. (OMIM:246450)
- Hyperuricemia (HP:0002149): The concentration of uric acid in the blood circulation is above the upper limit of normal. Evidence: IEA. (OMIM:246450)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 5/34. (PMID:28583327)
These phenotypes are associated with the disease 3-hydroxy-3-methylglutaric aciduria (OMIM:246450).