- Encephalopathy (HP:0001298, a Human Phenotype Ontology term): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Vertigo (HP:0002321, a Human Phenotype Ontology term): An abnormal sensation of spinning while the body is actually stationary. Evidence: PCS. (PMID:22152682)
- Dystonia (HP:0001332, a Human Phenotype Ontology term): 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: 3/5. (PMID:22152682)
- Seizure (HP:0001250, a Human Phenotype Ontology term): 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: 1/5. (PMID:22152682)
- Gait ataxia (HP:0002066, a Human Phenotype Ontology term): A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Hypotonia (HP:0001252, a Human Phenotype Ontology term): 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: 1/5. (PMID:22152682)
- Global brain atrophy (HP:0002283, a Human Phenotype Ontology term): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Infantile onset (HP:0003593, a Human Phenotype Ontology term): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/5. (PMID:22152682)
- Ataxia (HP:0001251, a Human Phenotype Ontology term): 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: PCS. (PMID:22152682)
- Lower limb spasticity (HP:0002061, a Human Phenotype Ontology term): Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Intention tremor (HP:0002080, a Human Phenotype Ontology term): A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger). Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Increased urine alpha-ketoglutarate concentration (HP:0012402, a Human Phenotype Ontology term): A greater than normal concentration of 2-oxoglutaric acid in the urine. Evidence: PCS. Frequency: 4/5. (PMID:22152682)
- Nystagmus (HP:0000639, a Human Phenotype Ontology term): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Childhood onset (HP:0011463, a Human Phenotype Ontology term): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 3/5. (PMID:22152682)
- Clonic seizure (HP:0020221, a Human Phenotype Ontology term): A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Lactic acidosis (HP:0003128, a Human Phenotype Ontology term): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: PCS. Frequency: 3/5. (PMID:22152682)
- Microcephaly (HP:0000252, a Human Phenotype Ontology term): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Truncal ataxia (HP:0002078, a Human Phenotype Ontology term): Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Delayed speech and language development (HP:0000750, a Human Phenotype Ontology term): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Gait disturbance (HP:0001288, a Human Phenotype Ontology term): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 3/10. (PMID:22152682)
- Developmental regression (HP:0002376, a Human Phenotype Ontology term): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Episodic ataxia (HP:0002131, a Human Phenotype Ontology term): Periodic spells of incoordination and imbalance, that is, episodes of ataxia typically lasting from 10 minutes to several hours or days. Evidence: PCS. Frequency: 2/5. (PMID:22152682)
- Dysarthria (HP:0001260, a Human Phenotype Ontology term): 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: PCS. Frequency: 1/5. (PMID:22152682)
- Loss of speech (HP:0002371, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Increased circulating lactate concentration (HP:0002151, a Human Phenotype Ontology term): 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: 2/5. (PMID:22152682)
- Global developmental delay (HP:0001263, a Human Phenotype Ontology term): 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: 2/5. (PMID:22152682)
- Increased CSF lactate (HP:0002490, a Human Phenotype Ontology term): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 2/5. (PMID:22152682)
- Dysphonia (HP:0001618, a Human Phenotype Ontology term): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Ophthalmoplegia (HP:0000602, a Human Phenotype Ontology term): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Left ventricular hypertrophy (HP:0001712, a Human Phenotype Ontology term): Enlargement or increased size of the heart left ventricle. Evidence: PCS. Frequency: 1/5. (PMID:22152682)
- Autosomal recessive inheritance (HP:0000007, a Human Phenotype Ontology term): 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:22152682)
- Spasticity (HP:0001257, a Human Phenotype Ontology term): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: PCS. Frequency: 2/5. (PMID:22152682)
These phenotypes are associated with the disease childhood encephalopathy due to thiamine pyrophosphokinase deficiency (OMIM:614458, an entry in Online Mendelian Inheritance in Man).