Phenotypes associated with the disease Fatal infantile lactic acidosis with methylmalonic aciduria (ORPHA:17):
- Methylmalonic acidemia (HP:0002912): The concentration of methylmalonic acid in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Obligate (HP:0040280). (ORPHA:17)
- Methylmalonic aciduria (HP:0012120): Increased concentration of methylmalonic acid in the urine. Evidence: TAS. Frequency: Obligate (HP:0040280). (ORPHA:17)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:17)
- 3-Methylglutaconic aciduria (HP:0003535): An increased amount of 3-methylglutaconic acid in the urine. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:17)
- Floppy infant (HP:0008947): Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:17)
- Abnormal circulating enzyme concentration or activity (HP:0012379): Concentration or activity of an enzyme is above or below the limits of normal in the blood circulation. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:17)
- Abnormal basal ganglia MRI signal intensity (HP:0012751): A deviation from normal signal on magnetic resonance imaging (MRI) of the basal ganglia. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:17)
- 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: Frequent (HP:0040282). (ORPHA:17)
- 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: Frequent (HP:0040282). (ORPHA:17)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- 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:17)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Decreased activity of mitochondrial complex IV (HP:0008347): A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Decreased activity of mitochondrial complex I (HP:0011923): A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- Decreased activity of mitochondrial complex III (HP:0011924): A reduction in the activity of the mitochondrial respiratory chain complex III, which is part of the electron transport chain in mitochondria. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:17)
- 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:17)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Short attention span (HP:0000736): Reduced attention span characterized by distractibility and impulsivity. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Hyperhidrosis (HP:0000975): Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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:17)
- Choreoathetosis (HP:0001266): Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Hypertrophic cardiomyopathy (HP:0001639): Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Hypothermia (HP:0002045): Reduced body temperature due to failed thermoregulation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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:17)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Unsteady gait (HP:0002317). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- 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:17)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Hyperkinetic movements (HP:0002487): Motor hyperactivity with excessive movement of muscles of the body as a whole. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Ragged-red muscle fibers (HP:0003200): An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Rhabdomyolysis (HP:0003201): Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Increased variability in muscle fiber diameter (HP:0003557): An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Abnormal mitochondrial shape (HP:0012087): An anomaly in the surface contour of mitochondria. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Increased intramyocellular lipid droplets (HP:0012240): An abnormal increase in intracellular lipid droplets In a muscle. The number and size of these drops can increase with somd disorders of lipid metabolism affecting muscle. See PMID 20691590 for histological images. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:17)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Orofacial cleft (HP:0000202): The presence of a cleft (gap, opening, or groove) in the oral cavity, including cleft of the upper lip and/or cleft of the palate. Cleft of the upper lip is visible as a groove or fissure in the lip, most frequently due to a congenital failure of the maxillary and median nasal processes to fuse. Cleft palate is characterized by a grooved depression or fissure in the roof of the mouth, most often resulting from a congenital failure of the palate to fuse properly. Clefts of the lip and palate can occur individually or together. It is preferable to code each defect separately. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Short femur (HP:0003097): An abnormal shortening of the femur. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Ethylmalonic aciduria (HP:0003219): The concentration of ethylmalonic acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Abnormal renal collecting system morphology (HP:0004742): An abnormality of the renal collecting system. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Short humerus (HP:0005792): Underdevelopment of the humerus. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Polydactyly (HP:0010442): A congenital anomaly characterized by the presence of supernumerary fingers or toes. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)
- Interrupted aortic arch (HP:0011611): Non-continuity of the arch of aorta with an atretic point or absent segment. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:17)