- 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: IEA. (OMIM:607483)
- Hypertonia (HP:0001276, a Human Phenotype Ontology term): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: IEA. (OMIM:607483)
- Mutism (HP:0002300, a Human Phenotype Ontology term): Complete lack of speech or verbal communication in a person despite attempts to engage in conversation. Mutism as a phenomena assumes the individual has previous capacity for speech and in the pediatric population it assumes that the person is past the age of typical language development. Evidence: PCS. Frequency: 1/2. (PMID:20065143)
- Lethargy (HP:0001254, a Human Phenotype Ontology term): 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: PCS. Frequency: 6/10. (PMID:9679779)
- Facial palsy (HP:0010628, a Human Phenotype Ontology term): Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form. Evidence: PCS. Frequency: 3/10. (PMID:9679779)
- Action tremor (HP:0002345, a Human Phenotype Ontology term): A tremor present when the limbs are active, either when outstretched in a certain position or throughout a voluntary movement. Evidence: PCS. Frequency: 3/10. (PMID:9679779)
- Inability to walk (HP:0002540, a Human Phenotype Ontology term): Incapability to ambulate. Evidence: PCS. Frequency: 2/2. (OMIM:607483)
- 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: 15/15. (PMID:9679779;PMID:26863430;PMID:20065143)
- 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: 10/15. (PMID:9679779;PMID:26863430;PMID:20065143)
- 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: 1/2. (PMID:20065143)
- Paraparesis (HP:0002385, a Human Phenotype Ontology term): Weakness or partial paralysis in the lower limbs. Evidence: IEA. (OMIM:607483)
- Rigidity (HP:0002063, a Human Phenotype Ontology term): Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Evidence: IEA. (OMIM:607483)
- Abnormal pyramidal tract morphology (HP:0002062, a Human Phenotype Ontology term): Any structural abnormality of the pyramidal tract, whose chief element, the corticospinal tract, is the only direct connection between the brain and the spinal cord. In addition to the corticospinal tract, the pyramidal system includes the corticobulbar, corticomesencephalic, and corticopontine tracts. Evidence: IEA. (OMIM:607483)
- Craniofacial dystonia (HP:0012179, a Human Phenotype Ontology term): A form of focal dystonia affecting the face and especially the jaw that is induced by the act of speaking. It is an involuntary contraction of the masticatory muscles, resulting in dysarthria or dysphagia. Evidence: TAS. (OMIM:607483)
- 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: IEA. (OMIM:607483)
- Irritability (HP:0000737, a Human Phenotype Ontology term): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: TAS. (OMIM:607483)
- Childhood onset (HP:0011463, a Human Phenotype Ontology term): Onset of disease at the age of between 1 and 5 years. Evidence: IEA. Frequency: 3/3. (PMID:26863430)
- Young adult onset (HP:0011462, a Human Phenotype Ontology term): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/2. (PMID:20065143)
- Fever (HP:0001945, a Human Phenotype Ontology term): Body temperature elevated above the normal range. Evidence: IEA. (OMIM:607483)
- Frequent falls (HP:0002359, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 1/3. (PMID:26863430)
- Axial hypotonia (HP:0008936, a Human Phenotype Ontology term): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: TAS. (OMIM:607483)
- Opisthotonus (HP:0002179, a Human Phenotype Ontology term): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: PCS. Frequency: 3/10. (PMID:9679779)
- Dysphagia (HP:0002015, a Human Phenotype Ontology term): Difficulty in swallowing. Evidence: PCS. Frequency: 2/2. (PMID:20065143)
- Juvenile onset (HP:0003621, a Human Phenotype Ontology term): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 11/12. (PMID:20065143;OMIM:607483)
- Confusion (HP:0001289, a Human Phenotype Ontology term): Lack of clarity and coherence of thought, perception, understanding, or action. Evidence: PCS. Frequency: 8/12. (PMID:9679779;PMID:20065143)
- Abnormal basal ganglia morphology (HP:0002134, a Human Phenotype Ontology term): Abnormality of the basal ganglia. Evidence: PCS. (PMID:9679779)
- Babinski sign (HP:0003487, a Human Phenotype Ontology term): 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: PCS. Frequency: 5/10. (PMID:9679779)
- Vomiting (HP:0002013, a Human Phenotype Ontology term): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 5/10. (PMID:9679779)
- Truncal titubation (HP:0030147, a Human Phenotype Ontology term): Tremor of the trunk in an anterior-posterior plane at 3-4 Hz. Evidence: PCS. Frequency: 2/10. (PMID:9679779)
- Developmental regression (HP:0002376, a Human Phenotype Ontology term): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 3/3. (PMID:26863430)
- 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: 8/10. (PMID:9679779)
- Cogwheel rigidity (HP:0002396, a Human Phenotype Ontology term): A type of rigidity in which a muscle responds with cogwheellike jerks to the use of constant force in bending the limb (i.e., it gives way in little, repeated jerks when the muscle is passively stretched). Evidence: PCS. Frequency: 9/10. (PMID:9679779)
- 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: TAS. Frequency: 2/20. (OMIM:607483)
- Loss of speech (HP:0002371, a Human Phenotype Ontology term). Evidence: PCS. Frequency: 2/2. (PMID:20065143)
- Tetraparesis (HP:0002273, a Human Phenotype Ontology term): Weakness of all four limbs. Evidence: PCS. Frequency: 6/10. (PMID:9679779)
- Chorea (HP:0002072, a Human Phenotype Ontology term): Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities. Evidence: PCS. Frequency: 2/10. (PMID:9679779)
- Ptosis (HP:0000508, a Human Phenotype Ontology term): 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: PCS. Frequency: 1/2. (PMID:20065143)
- Abnormal pyramidal sign (HP:0007256, a Human Phenotype Ontology term): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: PCS. Frequency: 2/2. (PMID:20065143)
- 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:15871139)
- Coma (HP:0001259, a Human Phenotype Ontology term): The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli. Evidence: PCS. Frequency: 10/10. (PMID:9679779)
- External ophthalmoplegia (HP:0000544, a Human Phenotype Ontology term): Paralysis of the external ocular muscles. Evidence: IEA. (OMIM:607483)
These phenotypes are associated with the disease biotin-responsive basal ganglia disease (OMIM:607483, an entry in Online Mendelian Inheritance in Man).