- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Abnormal spinal cord dorsal column morphology (HP:0011397): An abnormality of the dorsal columns, i.e., of the dorsal portion of the gray substance of the spinal cord. The dorsal column consists of the fasciculus gracilis and fasciculus cuneatus and itself is part of the dorsal funiculus. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:137898)
- 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: Frequent (HP:0040282). (ORPHA:137898)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Abnormal cerebellum morphology (HP:0001317): Any structural abnormality of the cerebellum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Progressive cerebellar ataxia (HP:0002073). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Abnormal speech pattern (HP:0002167): An abnormality in the sound (volume) or cadence (rate) of speech. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Progressive spasticity (HP:0002191): Spasticity that increases in degree with time. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Unsteady gait (HP:0002317). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Upper motor neuron dysfunction (HP:0002493): A functional anomaly of the upper motor neuron. The upper motor neurons are neurons of the primary motor cortex which project to the brainstem and spinal chord via the corticonuclear, corticobulbar and corticospinal (pyramidal) tracts. They are involved in control of voluntary movements. Dysfunction leads to weakness, impairment of fine motor movements, spasticity, hyperreflexia and abnormal pyramidal signs. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Spastic ataxia (HP:0002497). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Dysmyelinating leukodystrophy (HP:0006978). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137898)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Diminished deep tendon reflex (HP:0001315): A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Specific learning disability (HP:0001328): Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- 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: Occasional (HP:0040283). (ORPHA:137898)
- Impaired vibration sensation in the lower limbs (HP:0002166): A decrease in the ability to perceive vibration in the legs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Peripheral axonal neuropathy (HP:0003477): An abnormality characterized by disruption of the normal functioning of peripheral axons. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Impaired distal proprioception (HP:0006858): A loss or impairment of the sensation of the relative position of parts of the body and joint position occurring at distal joints. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Poor fine motor coordination (HP:0007010): An abnormality of the ability (skills) to perform a precise movement of small muscles with the intent to perform a specific act. Fine motor skills are required to mediate movements of the wrists, hands, fingers, feet, and toes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Leg muscle stiffness (HP:0008969). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Impaired visuospatial constructive cognition (HP:0010794): Reduced ability affecting mainly visuospatial cognition which may be tested using pattern construction (for example by Differential Ability Scales, which test a person's strengths and weaknesses across a range of intellectual abilities). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137898)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Slow saccadic eye movements (HP:0000514): An abnormally slow velocity of the saccadic eye movements. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Diplopia (HP:0000651): Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- 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: Very rare (HP:0040284). (ORPHA:137898)
- 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: Very rare (HP:0040284). (ORPHA:137898)
- 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: Very rare (HP:0040284). (ORPHA:137898)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Slurred speech (HP:0001350): Abnormal coordination of muscles involved in speech. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Truncal ataxia (HP:0002078): Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Spastic/hyperactive bladder (HP:0005340). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Impaired pursuit initiation and maintenance (HP:0007668). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
- Generalized limb muscle atrophy (HP:0009055): Generalized (unlocalized) atrophy affecting muscles of the limbs in both proximal and distal locations. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137898)
These phenotypes are associated with the disease Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (ORPHA:137898).