Phenotypes associated with the disease branched-chain keto acid dehydrogenase kinase deficiency (OMIM:614923):
- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 4/19. (PMID:36729635;PMID:22956686)
- Language impairment (HP:0002463): Language impairment is a deficit in comprehension or production of language that includes reduced vocabulary, limited sentence structure, or impairments in written or spoken communication. Language abilities are substantially and quantifiably below age expectations. Evidence: PCS. Frequency: 17/17. (PMID:36729635)
- 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: PCS. Frequency: 2/10. (PMID:36729635)
- 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: PCS. Frequency: 11/25. (PMID:36729635;PMID:22956686)
- 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: PCS. Frequency: 5/17. (PMID:36729635)
- 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: PCS. Frequency: 1/20. (PMID:36729635)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 4/6. (PMID:22956686)
- Interictal epileptiform activity (HP:0011182): Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure. Evidence: PCS. Frequency: 17/24. (PMID:36729635;PMID:22956686)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: PCS. Frequency: 1/1. (PMID:22956686)
- Dry skin (HP:0000958): Skin characterized by the lack of natural or normal moisture. Evidence: PCS. Frequency: 2/17. (PMID:36729635)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 2/6. (PMID:22956686)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: PCS. Frequency: 8/18. (PMID:36729635)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: PCS. Frequency: 11/19. (PMID:36729635)
- Restlessness (HP:0000711): A state of unease is characterized by diffuse motor activity or motion, which is subject to limited control, nonproductive, or disorganized behavior. Evidence: PCS. Frequency: 6/21. (PMID:36729635)
- Hyperactivity (HP:0000752): Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate. Evidence: PCS. Frequency: 5/21. (PMID:36729635)
- 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: PCS. Frequency: 22/22. (PMID:36729635;PMID:22956686)
- Progressive microcephaly (HP:0000253): Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms. Evidence: PCS. Frequency: 17/20. (PMID:36729635)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: PCS. Frequency: 12/15. (PMID:36729635)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/6. (PMID:22956686)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 5/20. (PMID:36729635)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: PCS. Frequency: 4/21. (PMID:36729635)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 9/21. (PMID:36729635)
- Global developmental delay (HP:0001263): 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: 27/27. (PMID:36729635;PMID:22956686)
- Decreased CSF isoleucine concentration (HP:0500194): Abnormally decreased levels of isoleucine in cerebrospinal fluid. Evidence: PCS. Frequency: 20/21. (PMID:36729635)
- Simple febrile seizure (HP:0011171): A short generalized seizure, of a duration of <15 min, not recurring within 24 h, occurring during a febrile episode not caused by an acute disease of the nervous system intracranial infection or severe metabolic disturbance. Evidence: PCS. Frequency: 3/3. (PMID:22956686)
- Decreased CSF leucine concentration (HP:0500190): Abnormally decreased levels of leucine in the cerebrospinal fluid. Evidence: PCS. Frequency: 19/21. (PMID:36729635)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: PCS. Frequency: 3/21. (PMID:36729635)
- Autistic behavior (HP:0000729): Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior. Evidence: PCS. Frequency: 20/25. (PMID:36729635;PMID:22956686)
- Autosomal recessive inheritance (HP:0000007): 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:22956686)
- Focal-onset seizure (HP:0007359): A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures. Evidence: PCS. Frequency: 1/21. (PMID:36729635)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: PCS. Frequency: 1/17. (PMID:36729635)
- Hyperkinetic movements (HP:0002487): Motor hyperactivity with excessive movement of muscles of the body as a whole. Evidence: PCS. Frequency: 1/20. (PMID:36729635)
- Generalized myoclonic seizure (HP:0002123): A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 1/18. (PMID:36729635)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: PCS. Frequency: 2/17. (PMID:36729635)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 26/26. (PMID:36729635;PMID:22956686)
- 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: PCS. Frequency: 15/16. (PMID:36729635)
- Inflammatory abnormality of the skin (HP:0011123): The presence of inflammation of the skin. That is, an abnormality of the skin resulting from the local accumulation of fluid, plasma proteins, and leukocytes. Evidence: PCS. Frequency: 3/17. (PMID:36729635)
- Thin upper lip vermilion (HP:0000219): Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). Evidence: PCS. Frequency: 4/21. (PMID:36729635)
- Decreased CSF valine concentration (HP:0500188): Any decreased amount from normal of valine in the cerebrospinal fluid. Evidence: PCS. Frequency: 20/21. (PMID:36729635)
- Hypoisoleucinemia (HP:0500144): The concentration of isoleucine in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 25/27. (PMID:36729635;PMID:22956686)
- Hypoleucinemia (HP:0500143): The concentration of leucine in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 26/27. (PMID:36729635;PMID:22956686)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 7/19. (PMID:36729635;PMID:22956686)
- Hypoplastic philtrum (HP:0005326): Underdevelopment of the philtrum. Evidence: PCS. Frequency: 2/21. (PMID:36729635)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 5/8. (PMID:36729635)
- Small forehead (HP:0000350): The presence of a forehead that is abnormally small. Evidence: PCS. Frequency: 3/21. (PMID:36729635)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: PCS. Frequency: 16/20. (PMID:36729635)
- Typical absence seizure (HP:0011147): A typical absence seizure is a type of generalized non-motor (absence) seizure characterized by its sudden onset, interruption of ongoing activities, a blank stare, possibly a brief upward deviation of the eyes. Usually the patient will be unresponsive when spoken to. Duration is a few seconds to half a minute with very rapid recovery. Although not always available, an EEG would usually show 3 Hz generalized epileptiform discharges during the event. Evidence: PCS. Frequency: 2/18. (PMID:36729635)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: PCS. Frequency: 10/21. (PMID:36729635)
- Coarse hair (HP:0002208): Hair shafts are rough in texture. Evidence: PCS. Frequency: 1/17. (PMID:36729635)
- Abnormal nasal bridge morphology (HP:0000422): Abnormality of the nasal bridge, which is the saddle-shaped area that includes the nasal root and the lateral aspects of the nose. It lies between the glabella and the inferior boundary of the nasal bone, and extends laterally to the inner canthi. Evidence: PCS. Frequency: 2/21. (PMID:36729635)
- Attention deficit hyperactivity disorder (HP:0007018): Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient. Evidence: PCS. Frequency: 4/18. (PMID:36729635)
- Hypovalinemia (HP:0500132): The concentration of valine in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 26/27. (PMID:36729635;PMID:22956686)