Phenotypes associated with the disease congenital disorder of glycosylation type 1EE with or without immunodeficiency (OMIM:621140):
- Poor head control (HP:0002421): Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months. Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- 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: PCS. Frequency: 1/1. (PMID:31775018)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- 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: 1/1. (PMID:38622837)
- 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: 1/1. (PMID:35637269)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Delayed ability to crawl (HP:0033128): A failure to achieve the ability to crawl at an appropriate developmental stage. Normal infant motor development is marked by a series of postural milestones including learning to crawl on hands and knees between the ages of 6 and 10 months. Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- Abnormally low T cell receptor excision circle level (HP:0031545): Reduced level of T cell receptor excision circle (TRECs) as measured by the TREC assay. Late in maturation, 70% of thymocytes that will ultimately express alpha/beta-T cell receptors form a circular DNA TREC from the excised TCRdelta gene that lies within the TCRalpha genetic locus. The circles are stable but do not increase following cell division and, therefore, become diluted as T cells proliferate. A quantitative polymerase chain reaction (PCR) reaction across the joint of the circular DNA provides the TREC copy number, a marker of newly-formed, antigenically-naïve thymic emigrant T cells. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Increased CD21low B cell proportion (HP:0033207): Increased proportion relative to B-lymphocytes of a subset of B lymphocytes characterized by dim/low levels of CD21, i.e., CD21-/low, in flow cytometry, and additionally enriched in autoreactive clones as determined for instance by clonse showing rheumatoid factor (anti-IgG) reactivity and antibodies recognizing cytoplasmic and to a lesser extent nuclear structures. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Thromboembolic stroke (HP:0001727): A cerebrovascular accident (stroke) that occurs because of thromboembolism. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- Decreased total lymphocyte count (HP:0001888): A reduced number of lymphocytes in the blood. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Recurrent oral herpes (HP:0410028): Recurrent episodes of oral herpes, typically characterized by blisters or ulcers on the gums, lips and/or tongue caused by herpes virus. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Decreased circulating IgG concentration (HP:0004315): An abnormally decreased level of immunoglobulin G (IgG) in blood. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Elevated erythrocyte sedimentation rate (HP:0003565): An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Cleft palate (HP:0000175): Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate). Evidence: PCS. Frequency: 1/2. (PMID:35637269;PMID:38622837)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- 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: 2/3. (PMID:35637269;PMID:31775018;PMID:38622837)
- Abnormal class-switched memory B cell proportion (HP:0030386): A deviation of the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM-/IgD-) in circulation relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA. Evidence: PCS. Frequency: 0/1. (PMID:31775018)
- Abnormal isoelectric focusing of serum transferrin (HP:0003160): Glycosylated transferrin concentrations can be measured in serum as a marker of N-linked glycosylation fidelity. 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. These terms are retained for historical reasons but for new annotations the precise glycosylation defect should be recorded. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Increased plasmablast proportion (HP:0032128): Abnormal increase of plasmablasts, commonly characterized as CD27+CD38hi and sometimes additionally as IgMlowCD24-, measured as percentage of total B cells in the blood, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Recurrent oral thrush (HP:0009098): Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Inverted CD4:CD8 ratio (HP:0033222): CD4:CD8 ratio less than 1, measured either as proportion of total CD3+ T cells, or in absolute numbers per microliter. These are usually measured within the TCR alpha/beta positive population. Normally there are relatively more CD4+ than CD8+ T cells. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- 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:31775018)
- 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: PCS. Frequency: 1/1. (PMID:35637269)
- Hip osteoarthritis (HP:0008843). Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Chronic diarrhea (HP:0002028): The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Decreased naive CD4+ T cell proportion (HP:0410378): The proportion of naive CD4 T cells relative to the total number of T cells is below the lower limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- Decreased naive CD8+ T cell proportion (HP:0410377): Abnormal decrease of the naive CD8+ T cell subpopulation, commonly characterized as CD45RA+, CD45RO-, or CD27+, measured as percentage of total CD8+ T cells in the blood, compared to a reference range for a given sex and age-group. These cells are sometimes also characterized as CD62L+ and CCR7+. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Increased circulating IgE concentration (HP:0003212): An abnormally increased overall level of immunoglobulin E in blood. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Abnormality of the liver (HP:0001392): An abnormality of the liver. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Abnormal total T cell number (HP:0011839): Abnormal increase or decrease of absolute number (either count per volume or proportion of total lymphocytes) of T cells or of a subset of T cells, commonly characterized as CD3+ lymphocytes, in the blood, compared to a reference range for a given sex and age-group. These may include both TCR alpha/beta and gamma/delta T cells. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Decreased antigen-specific T cell proliferation (HP:0031402): Impaired proliferation and expansion of a T cell population following activation by an antigenic stimulus. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Decreased total CD4+ T cell proportion (HP:0032218): Abnormal decrease of helper CD3+CD4+ T cells, measured as percentage of total CD3+ T cells in the blood, compared to a reference range for a given sex and age-group. These are usually measured within the TCR alpha/beta positive population. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Encephalomalacia (HP:0040197): Encephalomalacia is the softening or loss of brain tissue after cerebral infarction, cerebral ischemia, infection, craniocerebral trauma, or other injury. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 2/2. (PMID:31775018;PMID:38622837)
- Dehydration (HP:0001944). Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Recurrent pneumonia (HP:0006532): An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Hemiparesis (HP:0001269): Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Vasculitis (HP:0002633): Inflammation of blood vessel. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Choking episodes (HP:0030842): Incidents in which a piece of food or other objects get stuck in the upper airway and provoke coughing, gagging, inability to talk, and difficulty breathing. Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- 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: 1/1. (PMID:35637269)
- Wrist arthritis (HP:6001197): Inflammation of the wrist joint. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 1/1. (PMID:35637269)
- Abnormal circulating IgG concentration (HP:0410242): An abnormal deviation from normal levels of IgG immunoglobulin in blood. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Abnormal circulating IgM concentration (HP:0410243): An abnormal deviation from normal levels of IgM immunoglobulin in blood. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Abnormal circulating IgA concentration (HP:0410240): An abnormal deviation from normal levels of IgA immunoglobulin in blood. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Abnormal circulating IgE concentration (HP:0410241): An abnormal deviation from normal levels of IgE immunoglobulin in blood. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Knee osteoarthritis (HP:0005086). Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Abnormal total B cell count (HP:0010975): The absolute number of B cells in the blood, per microlitre is outside the limits of normal of the reference range for the appropriate sex and age-group. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Elevated circulating C-reactive protein concentration (HP:0011227): The concentration of C-reactive protein in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:31775018;PMID:38622837)
- Pineal cyst (HP:0012683): A glial uniloculated or multiloculated fluid-filled sac that either reside within or completely replace the pineal gland. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Abnormal total natural killer cell count (HP:0040089): Abnormal increase or decrease of total natural killer (NK) cells, commonly characterized as CD3-CD19- and CD16+ or CD56+ lymphocytes, in the blood, per microlitre, or altered NK cell phenotype, compared to a reference range for a given sex and age-group, measured ex vivo. Evidence: PCS. Frequency: 0/1. (PMID:35637269)
- Recurrent fever (HP:0001954): Periodic (episodic or recurrent) bouts of fever. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Drowsiness (HP:0002329): Abnormal feeling of sleepiness or difficulty staying awake. Evidence: PCS. Frequency: 1/1. (PMID:38622837)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: PCS. Frequency: 1/1. (PMID:31775018)
- Immunodeficiency (HP:0002721): Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance. Evidence: PCS. Frequency: 1/1. (PMID:35637269)