Phenotypes associated with the disease Methylmalonic acidemia with homocystinuria, type cblC (ORPHA:79282):
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79282)
- Megaloblastic anemia (HP:0001889): Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79282)
- Hyperhomocystinemia (HP:0002160): An increased concentration of homocystine in the blood. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79282)
- Methylmalonic acidemia (HP:0002912): The concentration of methylmalonic acid in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79282)
- Methylmalonic aciduria (HP:0012120): Increased concentration of methylmalonic acid in the urine. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79282)
- Elevated circulating palmitoleylcarnitine concentration (HP:0031544): The concentration palmitoleylcarnitine (hexadecenoylcarnitine or C16:1) in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79282)
- Glossitis (HP:0000206): Inflammation of the tongue. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Retinal degeneration (HP:0000546): A nonspecific term denoting progressive loss of the retinal pigment epithelium (RPE) and/or neurosensory retinal cells. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Macular pseudocoloboma (HP:0001116): A so-called macular coloboma is characterized by a sharply defined, usually excavated, area without neuroretina and RPE tissues in the central area of the fundus. This lesion is not related to classical colobomas associated with optic fissure closure defects. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Abnormal macular pigmentation (HP:0008002): Any deviation from the normal, uniform distribution or appearance of pigment within the macular region of the retina. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Stomatitis (HP:0010280): Stomatitis is an inflammation of the mucous membranes of any of the structures in the mouth. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- Glomerulopathy (HP:0100820): Inflammatory or noninflammatory diseases affecting the glomeruli of the nephron. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Abnormality of the nervous system (HP:0000707): An abnormality of the nervous system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Atypical behavior (HP:0000708): Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Personality changes (HP:0000751): An abnormal shift in patterns of thinking, acting, or feeling. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Dilated cardiomyopathy (HP:0001644): Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Hydrops fetalis (HP:0001789): The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Dehydration (HP:0001944). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Hypothermia (HP:0002045): Reduced body temperature due to failed thermoregulation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Respiratory distress (HP:0002098): Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Abnormal speech pattern (HP:0002167): An abnormality in the sound (volume) or cadence (rate) of speech. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Memory impairment (HP:0002354): An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Deep venous thrombosis (HP:0002625): Formation of a blot clot in a deep vein. The clot often blocks blood flow, causing swelling and pain. The deep veins of the leg are most often affected. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Ketonuria (HP:0002919): High levels of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the urine. Ketone bodies are insignificant in the blood and urine of normal individuals in the postprandial or overnight-fasted state. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Hypomethioninemia (HP:0003658): A decreased concentration of methionine in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Atrophy of the spinal cord (HP:0006827). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Poor fine motor coordination (HP:0007010): An abnormality of the ability (skills) to perform a precise movement of small muscles with the intent to perform a specific act. Fine motor skills are required to mediate movements of the wrists, hands, fingers, feet, and toes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Auditory hallucination (HP:0008765): Perception of sounds without auditory stimulus. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Peripheral demyelination (HP:0011096): A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Neurodevelopmental delay (HP:0012758): Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Periventricular white matter hyperintensities (HP:0030891): Areas of brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the cerebral ventricles. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Impaired executive functioning (HP:0033051): A disturbance of executive functioning, which is broadly defined as the set of abilities that allow for the planning, executing, monitoring, and self-correcting of goal-directed behavior while inhibiting task-irrelevant behavior. At least some degree of executive skill is needed to complete most cognitive tasks, and deficits in executive abilities are central to many clinical conditions, including fronto-temporal dementia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- Subdural hemorrhage (HP:0100309): Hemorrhage occurring between the dura mater and the arachnoid mater. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- Stroke (HP:0001297): Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- Pulmonary embolism (HP:0002204): An embolus (that is, an abnormal particle circulating in the blood) located in the pulmonary artery and thereby blocking blood circulation to the lung. Usually the embolus is a blood clot that has developed in an extremity (for instance, a deep venous thrombosis), detached, and traveled through the circulation before becoming trapped in the pulmonary artery. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- Severe demyelination of the white matter (HP:0007258): A severe loss of myelin from nerve fibers in the central nervous system. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- Abnormal brain morphology (HP:0012443): A structural abnormality of the brain, which has as its parts the forebrain, midbrain, and hindbrain. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)
- Delirium (HP:0031258): A state of sudden and severe confusion. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79282)