- 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. (PMID:18593870)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 3/4. (PMID:18593870)
- 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: 1/3. (PMID:20528888)
- 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: 4/8. (PMID:20528888;PMID:18593870)
- 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: 2/3. (PMID:20528888)
- Acrocyanosis (HP:0001063): Bluish discoloration of the skin of the hands or feet. Evidence: PCS. Frequency: 4/5. (PMID:18593870)
- 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: 7/8. (PMID:20528888;PMID:18593870)
- 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: 6/6. (PMID:20528888;PMID:18593870)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 8/8. (PMID:20528888;PMID:18593870)
- 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: IEA. (OMIM:602473)
- Elevated circulating butyrylcarnitine concentration (HP:0033446): Concentration of O-butyrylcarnitine in the blood circulation above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:20528888)
- Abnormality of extrapyramidal motor function (HP:0002071): A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless). Evidence: IEA. (OMIM:602473)
- Elevated circulating thiosulfate concentration (HP:6000757): The concentration of thiosulfate in the blood circulation is above the upper limit of normal. Evidence: PCS. (PMID:28933811)
- Focal T2 hyperintense basal ganglia lesion (HP:0007183): A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia. Evidence: PCS. Frequency: 1/2. (PMID:20528888)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 2/3. (PMID:20528888)
- Abnormal retinal vascular morphology (HP:0008046): A structural abnormality of retinal vasculature. Evidence: PCS. (OMIM:602473)
- 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:14732903)
- Petechiae (HP:0000967): Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae. Evidence: PCS. Frequency: 5/8. (PMID:20528888;PMID:18593870)
- Ethylmalonic aciduria (HP:0003219): The concentration of ethylmalonic acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 5/5. (PMID:18593870)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 2/3. (PMID:20528888)
- 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. (PMID:18593870)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: PCS. Frequency: 11/11. (PMID:20528888;PMID:18593870)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: PCS. Frequency: 6/6. (PMID:20528888;PMID:18593870)
- Chronic diarrhea (HP:0002028): The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks. Evidence: PCS. Frequency: 6/8. (PMID:20528888;PMID:18593870)
These phenotypes are associated with the disease ethylmalonic encephalopathy (OMIM:602473).