- Hyperkinetic movements (HP:0002487): Motor hyperactivity with excessive movement of muscles of the body as a whole. Evidence: PCS. Frequency: 12/12. (PMID:17287286)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: IEA. (OMIM:612073)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 12/13. (PMID:15877282;PMID:17287286)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: IEA. (OMIM:612073)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: IEA. (OMIM:612073)
- Aminoaciduria (HP:0003355): An increased concentration of an amino acid in the urine. Evidence: TAS. (OMIM:612073)
- 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: 12/12. (PMID:17287286)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 8/11. (PMID:17287286)
- 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: IEA. (OMIM:612073)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 1/2. (PMID:15877282)
- 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: 14/14. (PMID:15877282;PMID:17287286)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: PCS. Frequency: 1/2. (PMID:15877282)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/2. (PMID:15877282)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 12/12. (PMID:17287286)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 1/12. (PMID:17287286)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/12. (PMID:17287286)
- Irritability (HP:0000737): 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: PCS. Frequency: 1/2. (PMID:15877282)
- Decreased activity of mitochondrial respiratory chain (HP:0008972): Decreased activity of the mitochondrial respiratory chain. Evidence: IEA. (OMIM:612073)
- Facial diplegia (HP:0001349): Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy). Evidence: IEA. (OMIM:612073)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: IEA. (OMIM:612073)
- Hyperhidrosis (HP:0000975): Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. Evidence: PCS. Frequency: 4/12. (PMID:17287286)
- Methylmalonic acidemia (HP:0002912): The concentration of methylmalonic acid in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 5/5. (PMID:17287286)
- 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:612073)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: IEA. (OMIM:612073)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:612073)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 12/12. (PMID:17287286)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: IEA. (OMIM:612073)
- Abnormal basal ganglia morphology (HP:0002134): Abnormality of the basal ganglia. Evidence: IEA. (OMIM:612073)
- 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: 2/2. (PMID:15877282)
- 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: PCS. Frequency: 8/10. (PMID:15877282;PMID:17287286)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 4/4. (PMID:17287286)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: IEA. (OMIM:612073)
- Severe global developmental delay (HP:0011344): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: PCS. Frequency: 2/2. (PMID:15877282)
- 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: IEA. (OMIM:612073)
- Small for gestational age (HP:0001518): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 2/2. (PMID:15877282)
- Methylmalonic aciduria (HP:0012120): Increased concentration of methylmalonic acid in the urine. Evidence: PCS. Frequency: 10/10. (PMID:17287286)
- 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: PCS. Frequency: 1/2. (PMID:15877282)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: IEA. (OMIM:612073)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: IEA. (OMIM:612073)
- 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:15877282)
- Microcytic anemia (HP:0001935): A kind of anemia in which the volume of the red blood cells is reduced. Evidence: PCS. Frequency: 2/2. (PMID:15877282)
- Respiratory insufficiency due to muscle weakness (HP:0002747). Evidence: IEA. (OMIM:612073)
- 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: IEA. (OMIM:612073)
- Progressive encephalopathy (HP:0002448). Evidence: IEA. (OMIM:612073)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: IEA. (OMIM:612073)
- Loss of ability to walk in early childhood (HP:0008945). Evidence: IEA. (OMIM:612073)
These phenotypes are associated with the disease mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (OMIM:612073).