- 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:277400)
- Middle age onset (HP:0003596): A type of adult onset with onset of symptoms at the age of 40 to 60 years. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Cardiac arrest (HP:0001695): An abrupt loss of heart function. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Hemolytic-uremic syndrome (HP:0005575): A thrombotic microangiopathy with presence of non-immune, intravascular hemolytic anemia, thrombocytopenia and acute kidney injury. A vicious cycle of complement activation, endothelial cell damage, platelet activation, and thrombosis is the hallmark of the disease. Evidence: IEA. (OMIM:277400)
- 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:277400)
- Renal insufficiency (HP:0000083): A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism. Evidence: IEA. (OMIM:277400)
- 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:277400)
- Cystathioninuria (HP:0003153): An elevated urinary concentration of cystathionine. Evidence: IEA. (OMIM:277400)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 133/175. (PMID:16311595;PMID:29302025)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:277400)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:277400)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 11/172. (PMID:16311595)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: IEA. (OMIM:277400)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 4/172. (PMID:16311595)
- Megaloblastic anemia (HP:0001889): Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts). Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Hydrocephalus (HP:0000238): Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation. Evidence: IEA. (OMIM:277400)
- Tachycardia (HP:0001649): A rapid heartrate that exceeds the range of the normal resting heartrate for age. Evidence: PCS. Frequency: 2/3. (PMID:29302025)
- Hypotension (HP:0002615): Low Blood Pressure, vascular hypotension. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- 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:277400)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: IEA. (OMIM:277400)
- Bradycardia (HP:0001662): A slower than normal heart rate (in adults, slower than 60 beats per minute). Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Homocystinuria (HP:0002156): An increased concentration of homocystine in the urine. Evidence: IEA. (OMIM:277400)
- Cystathioninemia (HP:0003286): An increased concentration of cystathionine in the blood. Evidence: IEA. (OMIM:277400)
- 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: IEA. (OMIM:277400)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: IEA. (OMIM:277400)
- 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:277400)
- Dementia (HP:0000726): A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. Evidence: IEA. (OMIM:277400)
- 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:16311595)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: TAS. (OMIM:277400)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: IEA. (OMIM:277400)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: IEA. (OMIM:277400)
- Pallor (HP:0000980): Abnormally pale skin. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Cerebral cortical atrophy (HP:0002120): Atrophy of the cortex of the cerebrum. Evidence: IEA. (OMIM:277400)
- 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: PCS. Frequency: 3/3. (PMID:29302025)
- Abnormal vitamin B12 concentration (HP:0004341): The concentration of vitamin B12 (or one of its metabolites) in the blood circulation is outside the limits of normal. Evidence: PCS. Frequency: 0/3. (PMID:29302025)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Pigmentary retinopathy (HP:0000580): An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. Evidence: IEA. (OMIM:277400)
- Hyperhomocystinemia (HP:0002160): An increased concentration of homocystine in the blood. Evidence: PCS. Frequency: 2/3. (PMID:29302025)
- Thromboembolism (HP:0001907): The formation of a blood clot inside a blood vessel that subsequently travels through the blood stream from the site where it formed to another location in the body, generally leading to vascular occlusion at the distant site. Evidence: IEA. (OMIM:277400)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:277400)
- 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:277400)
- Reduced visual acuity (HP:0007663). Evidence: TAS. (OMIM:277400)
- Methylmalonic acidemia (HP:0002912): The concentration of methylmalonic acid in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 12/13. (PMID:29302025;OMIM:277400)
- Metabolic acidosis (HP:0001942): Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause. Evidence: IEA. (OMIM:277400)
- Decreased methionine synthase activity (HP:0003524): A reduction in methionine synthase activity. Evidence: PCS. Frequency: 3/3. (PMID:29302025)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 25/176. (PMID:16311595)
- Confusion (HP:0001289): Lack of clarity and coherence of thought, perception, understanding, or action. Evidence: IEA. (OMIM:277400)
- 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:277400)
- Nephropathy (HP:0000112): A nonspecific term referring to disease or damage of the kidneys. Evidence: IEA. (OMIM:277400)
- 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:277400)
- Long face (HP:0000276): Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective). Evidence: IEA. (OMIM:277400)
- 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: 1/3. (PMID:29302025)
- Hematuria (HP:0000790): The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine). Evidence: IEA. (OMIM:277400)
- Pulmonary arterial hypertension (HP:0002092): Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Delirium (HP:0031258): A state of sudden and severe confusion. Evidence: IEA. (OMIM:277400)
- Acute kidney injury (HP:0001919): Sudden loss of renal function, as manifested by decreased urine production, and a rise in serum creatinine or blood urea nitrogen concentration (azotemia). Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- 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: 1/3. (PMID:29302025)
- Methylmalonic aciduria (HP:0012120): Increased concentration of methylmalonic acid in the urine. Evidence: TAS. (OMIM:277400)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: IEA. (OMIM:277400)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: IEA. (OMIM:277400)
- Hypomethioninemia (HP:0003658): A decreased concentration of methionine in the blood. Evidence: PCS. Frequency: 1/3. (PMID:29302025)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: IEA. (OMIM:277400)
- Decreased total neutrophil count (HP:0001875): Abnormal decrease of absolute number of neutrophils in the blood, per microlitre, compared to a reference range for a given sex and age-group. Evidence: IEA. (OMIM:277400)
These phenotypes are associated with the disease methylmalonic aciduria and homocystinuria type cblC (OMIM:277400).