- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Moderate intellectual disability (HP:0002342): Moderate intellectual disability (ID) is defined as a type of ID characterized by moderately sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 35-49. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Hypotension (HP:0002615): Low Blood Pressure, vascular hypotension. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Severe intellectual disability (HP:0010864): Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Fatigue (HP:0012378): A subjective feeling of tiredness characterized by a lack of energy and motivation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Hypoglycemic coma (HP:0001325): Coma induced by low blood sugar. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Dilated cardiomyopathy (HP:0001644): Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Cardiac arrest (HP:0001695): An abrupt loss of heart function. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Acute pancreatitis (HP:0001735): A acute form of pancreatitis. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Hypothermia (HP:0002045): Reduced body temperature due to failed thermoregulation. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- Spastic hemiparesis (HP:0011099): Unilateral paresis (weakness) with spasticity of the affected muscles and increased tendon reflexes. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:20)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:20)
- Nonketotic hypoglycemia (HP:0001958). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:20)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:20)
- 3-Methylglutaric aciduria (HP:0003344): An abnormally increased level of 3-hydroxy-3-methylglutaric acid in the urine. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:20)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Recurrent hypoglycemia (HP:0001988): Recurrent episodes of decreased concentration of glucose in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Anorexia (HP:0002039): Lack of desire to eat (loss of appetite). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Hyperuricemia (HP:0002149): The concentration of uric acid in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Tachypnea (HP:0002789): Very rapid breathing. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Lipid accumulation in hepatocytes (HP:0006561). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Reye syndrome-like episodes (HP:0006582): Repeated occurrences of acute noninflammatory encephalopathy and fatty degenerative liver failure. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Prolonged prothrombin time (HP:0008151): Increased 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:20)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Edema (HP:0000969): An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Pallor (HP:0000980): Abnormally pale skin. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- 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. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Weight loss (HP:0001824): Reduction of total body weight. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Decreased total leukocyte count (HP:0001882): An abnormal decreased number of leukocytes in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Thrombocytosis (HP:0001894): Increased numbers of platelets in the peripheral blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Dehydration (HP:0001944). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Fever (HP:0001945): Body temperature elevated above the normal range. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Increased total leukocyte count (HP:0001974): An abnormal increase in the number of leukocytes in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:20)
These phenotypes are associated with the disease 3-hydroxy-3-methylglutaric aciduria (ORPHA:20).