- 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: 1/1. (PMID:18385497)
- Lethargy (HP:0001254): 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: IEA. (OMIM:277410)
- Moderate intellectual disability (HP:0002342): Moderate intellectual disability (ID) is defined as a type of ID characterized by moderately sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 35-49. Evidence: PCS. Frequency: 1/1. (PMID:18385497)
- Dysmetria (HP:0001310): A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements. Evidence: PCS. Frequency: 1/1. (PMID:18385497)
- 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: IEA. (OMIM:277410)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: IEA. (OMIM:277410)
- 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: 2/2. (PMID:18385497)
- Decreased methylmalonyl-CoA mutase activity (HP:0003210): An abnormality of Krebs cycle metabolism that is characterized by a decreased rate of methylmalonyl-CoA mutase activity. Evidence: IEA. (OMIM:277410)
- 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: IEA. (OMIM:277410)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: IEA. (OMIM:277410)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:277410)
- Hyperhomocystinemia (HP:0002160): An increased concentration of homocystine in the blood. Evidence: PCS. Frequency: 1/1. (PMID:18385497)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:277410)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/1. (PMID:18385497)
- Megaloblastic anemia (HP:0001889): Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts). Evidence: IEA. (OMIM:277410)
- Methylmalonic acidemia (HP:0002912): The concentration of methylmalonic acid in the blood circulation is above the upper limit of normal. Evidence: IEA. (OMIM:277410)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 1/1. (PMID:18385497)
- 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:277410)
- Decreased methionine synthase activity (HP:0003524): A reduction in methionine synthase activity. Evidence: IEA. (OMIM:277410)
- Decreased circulating adenosylcobalamin concentration (HP:0003145): The concentration of adenosylcobalam in the blood circulation is below the lower limit of normal. Adenosylcobalamin is one of the active forms of vitamin B12. Evidence: IEA. (OMIM:277410)
- Decreased circulating methylcobalamin concentration (HP:0003223): The concentration of methylcobalamin in the blood circulation is below the lower limit of normal. Methylcobalamin is a form of vitamin B12. Evidence: IEA. (OMIM:277410)
- Homocystinuria (HP:0002156): An increased concentration of homocystine in the urine. Evidence: PCS. Frequency: 3/3. (PMID:18385497)
- Spastic ataxia (HP:0002497). Evidence: IEA. (OMIM:277410)
- 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: 1/1. (PMID:18385497)
- 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: 1/1. (PMID:18385497)
- Ectopia lentis (HP:0001083): Dislocation or malposition of the crystalline lens of the eye. A partial displacement (or dislocation) of the lens is described as a subluxation of the lens, while a complete displacement is termed luxation of the lens. A complete displacement occurs if the lens is completely outside the patellar fossa of the lens, either in the anterior chamber, in the vitreous, or directly on the retina. If the lens is partially displaced but still contained within the lens space, then it is termed subluxation. Evidence: PCS. Frequency: 0/1. (PMID:18385497)
- 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: PCS. Frequency: 1/1. (PMID:18385497)
- Methylmalonic aciduria (HP:0012120): Increased concentration of methylmalonic acid in the urine. Evidence: PCS. Frequency: 3/3. (PMID:18385497)
- 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:18385497)
- Increased mean corpuscular volume (HP:0005518): Larger than normal size of erythrocytes. Evidence: PCS. Frequency: 2/2. (PMID:18385497)
- Hypomethioninemia (HP:0003658): A decreased concentration of methionine in the blood. Evidence: IEA. (OMIM:277410)
- Horizontal nystagmus (HP:0000666): Nystagmus consisting of horizontal to-and-fro eye movements. Evidence: PCS. Frequency: 1/1. (PMID:18385497)
These phenotypes are associated with the disease methylmalonic aciduria and homocystinuria type cblD (OMIM:277410).