Phenotypes associated with the disease PMM2-congenital disorder of glycosylation (OMIM:212065):
- Premature ovarian insufficiency (HP:0008209): Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian insuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea. Evidence: IEA. (OMIM:212065)
- Thrombocytosis (HP:0001894): Increased numbers of platelets in the peripheral blood. Evidence: IEA. (OMIM:212065)
- 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. (OMIM:212065)
- 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: 5/20. (PMID:11134235)
- 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: 19/23. (PMID:11343337;PMID:11134235)
- 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: PCS. Frequency: 12/13. (PMID:11343337;OMIM:212065)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 19/23. (PMID:11343337;PMID:11134235)
- Hypoalbuminemia (HP:0003073): The concentration of albumin in the blood circulation is below the lower limit of normal. Evidence: IEA. (OMIM:212065)
- Reduced factor XI activity (HP:0001929): Decreased activity of coagulation factor XI. Factor XI, also known as plasma thromboplastin antecedent, is a serine proteinase that activates factor IX. Evidence: IEA. (OMIM:212065)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:212065)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: TAS. (OMIM:212065)
- Esodeviation (HP:0020045): A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally. Evidence: PCS. Frequency: 2/3. (PMID:11343337)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 4/20. (PMID:11134235)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: TAS. Frequency: 20/20. (OMIM:212065)
- Proximal tubulopathy (HP:0000114): Dysfunction of the proximal tubule, which is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle. Evidence: IEA. (OMIM:212065)
- Rod-cone dystrophy (HP:0000510): An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones. Evidence: IEA. (OMIM:212065)
- Decreased circulating IgG concentration (HP:0004315): An abnormally decreased level of immunoglobulin G (IgG) in blood. Evidence: IEA. (OMIM:212065)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 2/20. (PMID:11134235)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:212065)
- Type I transferrin isoform profile (HP:0003642): Abnormal transferrin isoform profile consistent with a type I congenital disorder of glycosylation. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II. Evidence: PCS. Frequency: 23/23. (PMID:11343337;PMID:11134235)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: IEA. (OMIM:212065)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- Dilated fourth ventricle (HP:0002198): An abnormal dilatation of the fourth cerebral ventricle. Evidence: PCS. Frequency: 2/3. (PMID:11343337)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- 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: 21/23. (PMID:11343337;PMID:11134235)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: IEA. (OMIM:212065)
- Edema (HP:0000969): An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Evidence: PCS. Frequency: 2/20. (PMID:11134235)
- Abnormal subcutaneous fat tissue distribution (HP:0007552). Evidence: IEA. (OMIM:212065)
- 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: IEA. (OMIM:212065)
- Reduced antithrombin III activity (HP:0001976): An abnormality of coagulation related to a decreased concentration of antithrombin-III. Evidence: IEA. (OMIM:212065)
- Almond-shaped palpebral fissure (HP:0007874): A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point. Evidence: PCS. Frequency: 3/3. (PMID:11343337)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: TAS. (OMIM:212065)
- 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: IEA. (OMIM:212065)
- Pericardial effusion (HP:0001698): Accumulation of fluid within the pericardium. Evidence: IEA. (OMIM:212065)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: IEA. (OMIM:212065)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- 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: 1/3. (PMID:11343337)
- Nephrotic syndrome (HP:0000100): Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia. Evidence: IEA. (OMIM:212065)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- Polyneuropathy (HP:0001271): A generalized disorder of peripheral nerves. Evidence: IEA. (OMIM:212065)
- Hepatic fibrosis (HP:0001395): The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process. Evidence: PCS. Frequency: 4/4. (PMID:11134235)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 12/20. (PMID:11134235)
- Nonimmune hydrops fetalis (HP:0001790): A type of hydrops fetalis in which there is no identifiable circulating antibody to red blood cell antigens . Evidence: IEA. (OMIM:212065)
- Enlarged cisterna magna (HP:0002280): Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- Intention tremor (HP:0002080): A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger). Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- Prolonged prothrombin time (HP:0008151): Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT. Evidence: TAS. (OMIM:212065)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. Frequency: 13/20. (OMIM:212065)
- Hypergonadotropic hypogonadism (HP:0000815): Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay. Evidence: IEA. (OMIM:212065)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: IEA. (OMIM:212065)
- 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: TAS. (OMIM:212065)
- Pericarditis (HP:0001701): Inflammation of the sac-like covering around the heart (pericardium). Evidence: PCS. Frequency: 5/20. (PMID:11134235)
- Thin upper lip vermilion (HP:0000219): Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). Evidence: IEA. (OMIM:212065)
- 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: IEA. (OMIM:212065)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/3. (PMID:11343337)
- Prolonged partial thromboplastin time (HP:0003645): Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms. Evidence: IEA. (OMIM:212065)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. Frequency: 2/3. (PMID:11343337)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: PCS. Frequency: 5/20. (PMID:11134235)
- Olivopontocerebellar hypoplasia (HP:0006955): Hypoplasia of the cerebellum, pontine nuclei, and inferior olivary nucleus. Evidence: IEA. (OMIM:212065)
- Reduced tissue phosphomannomutase activity (HP:6000781): Activity of the enzyme phosphomannomutase (EC 5.4.2.8) in tissues below the lower limit of normal. The activity can be measured in multiple tissues including leukocytes, fibroblasts, and liver. Evidence: PCS. Frequency: 3/3. (PMID:11343337)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. Frequency: 2/3. (PMID:11343337)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: PCS. Frequency: 18/20. (PMID:11134235)
- Hypocholesterolemia (HP:0003146): An decreased concentration of cholesterol in the blood. Evidence: IEA. (OMIM:212065)
- 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: 4/20. (PMID:11134235)
- Abnormality of the amniotic fluid (HP:0001560): Abnormality of the amniotic fluid, which is the fluid contained in the amniotic sac surrounding the developing fetus. Evidence: IEA. (OMIM:212065)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 11/20. (PMID:11134235)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: PCS. Frequency: 0/3. (PMID:11343337)
- Steatorrhea (HP:0002570): Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats. Evidence: PCS. Frequency: 1/18. (PMID:11134235)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: IEA. (OMIM:212065)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: PCS. Frequency: 1/20. (PMID:11134235)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: IEA. (OMIM:212065)
- Villous atrophy (HP:0011473): The enteric villi are atrophic or absent. Evidence: PCS. Frequency: 2/4. (PMID:11134235)
- Renal cyst (HP:0000107): A fluid filled sac in the kidney. Evidence: PCS. Frequency: 11/16. (PMID:11134235)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: IEA. (OMIM:212065)
- Cardiomyopathy (HP:0001638): A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Evidence: PCS. Frequency: 2/20. (PMID:11134235)
- Decreased circulating IgA concentration (HP:0002720): Decreased levels of immunoglobulin A (IgA). Evidence: IEA. (OMIM:212065)
- Stroke-like episode (HP:0002401): No consensus exists on what a stroke-like episode is, but these episodes can be functionally defined as a new neurological deficit, occurring with or without the context of seizures, which last longer than 24 hours. Evidence: IEA. (OMIM:212065)