- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: PCS. (PMID:17921179)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- 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: IEA. (OMIM:271245)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: IEA. (OMIM:271245)
- Distal amyotrophy (HP:0003693): Muscular atrophy affecting muscles in the distal portions of the extremities. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- 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: 2/2. (PMID:17921179)
- 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: 1/2. (PMID:17921179)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Fiber type grouping (HP:0033685): An abnormal distribution of muscle fiber types in muscle tissue. Human skeletal muscle contains at least two fiber types recognizable by histochemical techniques. In transverse sections of normal skeletal muscle, type 1 and type 2 fibers are distributed in a random fashion. Grouping of fibers of the same type can be seen in certain peripheral neuropathies, thought to be due to reinnervation of denervated muscle fibers by sprouting axons. With grouping, motor units enlarge. The fibers of a motor unit, which are normally scattered, come to lie adjacent to one another. Histochemical examination shows groups of muscle fibers of the same histochemical type. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- Sensory axonal neuropathy (HP:0003390): An axonal neuropathy of peripheral sensory nerves. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Epilepsia partialis continua (HP:0012847): Epilepsia partialis continua (also called Kojevnikov's or Kozhevnikov's epilepsia) is a type of focal motor status epilepticus characterized by repeated stereotyped simple motor manifestations such as jerks, typically of a limb or the face, recurring every few seconds or minutes for extended periods (days or years). Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- Hypergonadotropic hypogonadism (HP:0000815): Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay. Evidence: IEA. (OMIM:271245)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- 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: IEA. (OMIM:271245)
- Atrophy/Degeneration affecting the brainstem (HP:0007366). Evidence: TAS. (OMIM:271245)
- Cerebellar cortical atrophy (HP:0008278): Atrophy (wasting) of the cerebellar cortex. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: IEA. (OMIM:271245)
- 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: IEA. (OMIM:271245)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: IEA. (OMIM:271245)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:17921179)
- Decreased number of large peripheral myelinated nerve fibers (HP:0003387): A reduced number of large myelinated nerve fibers. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Status epilepticus (HP:0002133): Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- 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: PCS. Frequency: 1/2. (PMID:17921179)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Migraine (HP:0002076): Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms. Evidence: IEA. (OMIM:271245)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Excessive daytime somnolence (HP:0001262): A state of abnormally strong desire for sleep during the daytime. Evidence: IEA. (OMIM:271245)
- Psychosis (HP:0000709): A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis. Evidence: IEA. (OMIM:271245)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- 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:16135556)
- Epileptic encephalopathy (HP:0200134): A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death. Evidence: TAS. (OMIM:271245)
- 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: IEA. (OMIM:271245)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Athetosis (HP:0002305): A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
- Involuntary movements (HP:0004305): Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face. Evidence: PCS. Frequency: 2/2. (PMID:17921179)
These phenotypes are associated with the disease mitochondrial DNA depletion syndrome 7 (hepatocerebral type) (OMIM:271245).