Phenotypes associated with the disease Pyruvate carboxylase deficiency (ORPHA:3008):
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Generalized clonic seizure (HP:0011169): Generalized clonic seizure is a type of generalized motor seizure characterized by sustained bilateral jerking, either symmetric or asymmetric, that is regularly repetitive and involves the same muscle groups. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Cerebellar gliosis (HP:0012698): Focal proliferation of glial cells in the cerebellum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Cerebral white matter atrophy (HP:0012762): The presence of atrophy (wasting) of the cerebral white matter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Abnormal temper tantrums (HP:0025160): Temper tantrums are brief episodes of extreme, unpleasant, and sometimes aggressive behaviors in response to frustration or anger, which are a normal part of development in toddlers. Temper tantrums that occur more frequently in a given time and/or are more severe in symptomatology and/or longer in duration and/or inappropriate for the given age compared to a temper tantrum that naturally occurs as a part of the developmental process are classified as abnormal temper tantrums. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Delayed ability to sit (HP:0025336): A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Tip-toe gait (HP:0030051): An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Hyperintensity of cerebral white matter on MRI (HP:0030890): A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Dyskinesia (HP:0100660): A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- 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: Very rare (HP:0040284). (ORPHA:3008)
- Recurrent hand flapping (HP:0100023): A type of repetitive behavior in which the affected individual repeatedly waves the hands and/or arms rhythmically. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:3008)
- 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: Very frequent (HP:0040281). (ORPHA:3008)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:3008)
- Elevated lactate:pyruvate ratio (HP:0032653): An abnormal increase in the molar ratio of lactate to pyruvate in the blood circulation. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:3008)
- 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:3008)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- 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: Frequent (HP:0040282). (ORPHA:3008)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Hyperlysinemia (HP:0002161): The concentration of lysine in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Increased circulating pyruvate concentration (HP:0003542): The concentration of pyruvate in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Lacticaciduria (HP:0003648): An increased concentration of lactic acid in the urine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Hyperprolinemia (HP:0008358): The concentration of proline in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Elevated plasma citrulline (HP:0011966): An increased concentration of citrulline in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Increased caudate lactate level (HP:0012644): An elevated concentration of lactate in the caudate nucleus. This finding can be elicited by magnetic resonance spectroscopy imaging. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Elevated brain choline level by MRS (HP:0012706): An increase in the level of choline-containing compounds in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Elevated brain lactate level by MRS (HP:0012707): An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Reduced brain N-acetyl aspartate level by MRS (HP:0012708): A decrease in the level of N-acetyl aspartate in the brain identified by magnetic resonance spectroscopy (MRS). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Neurodevelopmental delay (HP:0012758): Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Hyperketonemia (HP:0410175): An increase in the level of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Hypoglutaminemia (HP:0500147): The concentration of glutamine in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Hyperglutamatemia (HP:0500149): Concentration of glutamate in the blood circulation above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Hypertaurinemia (HP:0500181): An increased amount of taurine in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Decreased CSF glutamine concentration (HP:0500198): Abnormally decreased levels of glutamine in cerebrospinal fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Increased CSF glutamate concentration (HP:0500200): Abnormally increased levels of glutamic acid in cerebrospinal fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Abnormal CSF pyruvate family amino acid concentration (HP:0500231): Any deviation from the normal concentration of pyruvate-family amino acids in the cerebrospinal fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Increased CSF alanine concentration (HP:0500233): Abnormally increased levels of alanine in cerebrospinal fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Increased CSF citrulline concentration (HP:0500246): Abnormally increased levels of citrulline in cerebrospinal fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:3008)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Compulsive behaviors (HP:0000722): Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- 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: Occasional (HP:0040283). (ORPHA:3008)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- 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: Occasional (HP:0040283). (ORPHA:3008)
- 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: Occasional (HP:0040283). (ORPHA:3008)
- Excessive daytime somnolence (HP:0001262): A state of abnormally strong desire for sleep during the daytime. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Dehydration (HP:0001944). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Anorexia (HP:0002039): Lack of desire to eat (loss of appetite). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Poor speech (HP:0002465). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Tachypnea (HP:0002789): Very rapid breathing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Abnormal pattern of respiration (HP:0002793): An anomaly of the rhythm or depth of breathing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Hyperglycemia (HP:0003074): An increased concentration of glucose in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Hypernatremia (HP:0003228): The concentration of sodium in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Neonatal hyperbilirubinemia (HP:0003265): A type of hyperbilirubinemia with neonatal onset. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- CNS hypomyelination (HP:0003429): Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Basal ganglia gliosis (HP:0006999): Focal proliferation of glial cells in the basal ganglia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)
- Periventricular cysts (HP:0007109). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:3008)