- Spongiosis (HP:6001166): Spongiosis refers to the increased intercellular edema in the epidermis resulting in the pulling away of the keratinocytes from their surrounding desmosomes. Histologically, the spongiotic tissue reaction pattern involves the accumulation of fluid in the intercellular spaces of the epidermis, making the desmosomes junctions more easy to appreciate. Parakeratosis forms above the areas of spongiosis. The foci of spongiosis can be microscopic to grossly identifiable clinically with vesicles or bullae. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Abnormal erythrocyte sedimentation rate (HP:0025021): A deviation from normal range of the erythrocyte sedimentation rate (ESR), 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. A decreased ESR may be seen in polycythemia or in certain blood diseases in which red blood cells have an irregular or smaller shape that causes slower settling. Evidence: PCS. Frequency: 0/1. (PMID:29537367)
- Colitis (HP:0002583): Colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine (colon, cecum and rectum). Colitides may be acute and self-limited or chronic, and broadly fit into the category of digestive diseases. Evidence: PCS. Frequency: 1/6. (PMID:36662884)
- Decreased memory B cell proportion (HP:0030374): A reduction in the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV). Evidence: PCS. Frequency: 2/2. (PMID:36662884)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 10/10. (PMID:36917008;PMID:36662884)
- Increased memory CD8+ T cell proportion (HP:0410392): Abnormal increase of the memory 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. Evidence: PCS. Frequency: 3/3. (PMID:36917008)
- Increased memory CD4+ T cell proportion (HP:0410391): Abnormal increase of the memory CD4+ T cell subpopulation, commonly characterized as CD45RA-, CD45RO+, or CD27-, measured as percentage of total CD4+ T cells in the blood, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 3/3. (PMID:36917008)
- Abnormal circulating C-reactive protein concentration (HP:0032436): Any deviation from the normal concentration of C-reactive protein in the blood circulation. Evidence: PCS. Frequency: 0/1. (PMID:29537367)
- 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: 3/3. (PMID:36917008)
- Unusual molluscum contagiosum (HP:0032163): Molluscum contagiosum is a cutaneous viral infection that is commonly observed in both healthy and immunocompromised children. The infection is caused by a member of the Poxviridae family, the molluscum contagiosum virus. Molluscum contagiosum presents as single or multiple small white or flesh-colored papules that typically have a central umbilication. The central umbilication may be difficult to observe in young children and, instead, may bear an appearance similar to an acneiform eruption. The lesions vary in size (from 1 mm to 1 cm in diameter) and are painless, although a subset of patients report pruritus in the area of infection. On average, 11-20 papules appear on the body during the course of infection and generally remains a self-limiting disease. However, in immunosuppressed patients, molluscum contagiosum can be a severe infection with hundreds of lesions developing on the body. Extensive eruption is indicative of an advanced immunodeficiency state. Evidence: PCS. Frequency: 1/1. (PMID:36917008)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/1. (PMID:29537367)
- Increased transitional B cell proportion (HP:0030381): Abnormal increase of the transitional B cell subpopulation, commonly characterized as CD27-CD24hiCD38hi or CD27-IgMhiCD38hi, 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: 2/2. (PMID:36662884)
- Premature graying of hair (HP:0002216): Development of gray hair at a younger than normal age. Evidence: PCS. Frequency: 3/3. (PMID:36917008)
- Bronchoconstriction (HP:4000007): Tightening of smooth muscle surrounding the bronchi and bronchioles with consequent wheezing and shortness of breath. Evidence: PCS. Frequency: 2/6. (PMID:36662884)
- Arthritis (HP:0001369): Inflammation of a joint. Evidence: PCS. Frequency: 1/2. (PMID:29537367;PMID:36662884)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Inflammation of the large intestine (HP:0002037): Inflammation, or an inflammatory state in the large intestine. Evidence: PCS. Frequency: 1/1. (PMID:36917008)
- BCGitis (HP:0020086): Local or regional infection with Bacillus Calmette-Guerin (BCG) following vaccination. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Decreased class-switched memory B cell proportion (HP:0030388): A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) 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: 3/4. (PMID:36662884)
- Bronchiectasis (HP:0002110): Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways. Evidence: PCS. Frequency: 1/6. (PMID:36662884)
- Epidermal acanthosis (HP:0025092): Diffuse hypertrophy or thickening of the stratum spinosum of the epidermis (prickle cell layer of the skin). Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Synovial lining hyperplasia (HP:0005186): Synovial hyperplasia involves proliferation of mesenchymal stromal/stem cells and leads to synovial thickening, which can be observed radiographically. Evidence: PCS. Frequency: 1/1. (PMID:29537367)
- Hypoxemia (HP:0012418): An abnormally low level of blood oxygen. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Bulging fontanelle (HP:6000647): An outward curving of a fontanelle, which occurs when fluid builds up in the brain or the brain swells, causing increased pressure inside the skull. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Recurrent pharyngitis (HP:0100776): Increased susceptibility to pharyngitis, as manifested by recurrent episodes of pharyngeal infection that are unusual in frequency or severity for a healthy individual of the same age. Evidence: PCS. Frequency: 2/2. (PMID:36917008)
- Severe varicella zoster infection (HP:0032170): An unusually severe form of varicella zoster virus (VZV) infection. In the majority of the cases, especially in children, varicella is a very mild infection characterized by skin lesions, low grade fever and malaise. Severe infection is characterized by manifestations including VZV pneumonia, hepatitis, meningitis, and disseminated varicella. Evidence: PCS. Frequency: 1/1. (PMID:36917008)
- Arthralgia (HP:0002829): Joint pain. Evidence: PCS. Frequency: 1/1. (PMID:29537367)
- Granuloma (HP:0032252): A compact, organized collection of mature mononuclear phagocytes, which may be but is not necessarily accompanied by accessory features such as necrosis. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Decreased circulating total IgG concentration (HP:0032132): A reduction beneath the normal level of total immunoglobulin G (IgG) in the blood. Evidence: PCS. Frequency: 7/7. (PMID:36662884;PMID:29408330)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 2/2. (PMID:36917008)
- Eczematoid dermatitis (HP:0000964): Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- 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:29408330)
- Papule (HP:0200034): A circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Abdominal pain (HP:0002027): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Autosomal dominant inheritance (HP:0000006): 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: PCS. (PMID:36917008)
- 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: 5/9. (PMID:36917008;PMID:36662884)
- 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: 3/3. (PMID:36917008)
- Viremia (HP:0020071): The presence of virus in the blood. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Increased total CD4+ T cell proportion (HP:0032219): Abnormal increase 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: 1/3. (PMID:36662884)
- Decreased circulating IgE concentration (HP:0005479): An abnormally decreased level of immunoglobulin E (IgE) in blood. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Parakeratosis (HP:0001036): Abnormal formation of the keratinocytes of the epidermis characterized by persistence of nuclei, incomplete formation of keratin, and moistness and swelling of the keratinocytes. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- 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: 3/3. (PMID:36917008)
- Persistent EBV viremia (HP:0020072): Persistent or recurrent detection of Epstein-Barr virus (EBV) in the blood that occurs in the context of unusual susceptibility to infection. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Mastoiditis (HP:0000265): Infection of the mastoid air cells, arising as a complication of otitis media or occurring in the context of unusual susceptibility to infection. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Recurrent herpes (HP:0005353): Increased susceptibility to herpesvirus, as manifested by recurrent episodes of herpesvirus. Evidence: PCS. Frequency: 1/1. (PMID:36917008)
- Protracted diarrhea (HP:0004385). Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/6. (PMID:36662884)
- Erythema (HP:0010783): Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Unusual fungal nail infection (HP:0012203): Increased susceptibility to fungal infection of the nail apparatus (onychomycosis), as manifested by recurrent or severe infection of the nail plate, nail bed, or nail matrix caused by fungal organisms. Causative agents include dermatophytes (Trichophyton species) and Candida species. Evidence: PCS. Frequency: 3/7. (PMID:36917008;PMID:36662884)
- Unusual bronchiolitis (HP:0011950): Increased susceptibility to bronchiolitis (inflammation of the bronchioles) as manifested by recurrent or severe epsiodes of bronchiolitis. Evidence: PCS. Frequency: 1/5. (PMID:36662884)
- 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: 1/3. (PMID:36662884)
- Nontuberculous mycobacterial pulmonary infection (HP:0032261): An infection of the lung caused by environmental mycobacteria. Such infections can occur in individuals with predisposing lung disease or immune disease. Evidence: PCS. Frequency: 1/7. (PMID:36662884)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 0/1. (PMID:36662884)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Hyperhidrosis (HP:0000975): Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Lymphadenopathy (HP:0002716): Enlargement (swelling) of a lymph node. Evidence: PCS. Frequency: 1/6. (PMID:36662884)
- Respiratory failure (HP:0002878): A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits. Evidence: PCS. Frequency: 1/6. (PMID:36662884)
- Pneumocystis jirovecii pneumonia (HP:0020102): An opportunistic disease caused by invasion of unicellular fungus Pneumocystis jirovecii. Transmission of P. jirovecii cysts takes place through the airborne route, and usually, its presence in lungs is asymptomatic. However, people with impaired immunity, especially those with CD4+ T cell count below 200/microliter, are still at risk of the development of Pneumocystis pneumonia due to P. jirovecii invasion. Symptoms induced by this disease are not specific: progressive dyspnea, non-productive cough, low-grade fever, arterial partial pressure of oxygen below 65 mmHg, and chest radiographs demonstrating bilateral, interstitial shadowing. Evidence: PCS. Frequency: 6/7. (PMID:36662884)
- Recurrent pneumonia (HP:0006532): An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. Evidence: PCS. Frequency: 2/2. (PMID:36662884)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 1/6. (PMID:36662884)
- Papillary dermal edema (HP:6000263): Swelling due to fluid acculuation of the papillary dermis. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Decreased circulating IgM concentration (HP:0002850): An abnormally decreased level of immunoglobulin M (IgM) in blood. Evidence: PCS. Frequency: 7/7. (PMID:36662884;PMID:29408330)
- Increased total eosinophil count (HP:0001880): Increased count of eosinophils in the blood. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Agammaglobulinemia (HP:0004432): A lasting absence of total IgG and total IgA and total IgM in the blood circulation, whereby at most trace quantities can be measured. Evidence: PCS. Frequency: 4/4. (PMID:36662884)
- Sinus tachycardia (HP:0011703): Heart rate of greater than 100 beats per minute. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Abnormal lymphocyte proliferation (HP:0031378): Any abnormality in the multiplication or reproduction of lymphocytes, which results in the expansion of a cell population. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Hepatitis (HP:0012115): Inflammation of the liver. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Duodenitis (HP:0033117): Inflammation of the lining of the upper small intestine (duodenum). Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Recurrent sinusitis (HP:0011108): A recurrent form of sinusitis. Evidence: PCS. Frequency: 2/6. (PMID:36662884)
- Decreased total B cell count (HP:0010976): The absolute number of B cells in the blood, per microlitre is below the lower limit of normal of the reference range for the appropriate sex and age-group. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Adenoiditis (HP:0031458): An inflammation of the adenoid tissue. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Conjunctivitis (HP:0000509): Inflammation of the conjunctiva. Evidence: PCS. Frequency: 2/2. (PMID:36917008)
- 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: 0/3. (PMID:36917008)
- Recurrent fever (HP:0001954): Periodic (episodic or recurrent) bouts of fever. Evidence: PCS. Frequency: 1/1. (PMID:29408330)
- Skin rash (HP:0000988): A red eruption of the skin. Evidence: PCS. Frequency: 1/1. (PMID:36662884)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: PCS. Frequency: 2/2. (PMID:36662884)
- Hepatosplenomegaly (HP:0001433): Simultaneous enlargement of the liver and spleen. Evidence: PCS. Frequency: 1/1. (PMID:36917008)
- Decreased circulating IgA concentration (HP:0002720): Decreased levels of immunoglobulin A (IgA). Evidence: PCS. Frequency: 7/7. (PMID:36662884;PMID:29408330)
- Panhypogammaglobulinemia (HP:0003139): A reduction in the circulating levels of all the major classes of immunoglobulin. is characterized by profound decreases in all classes of immunoglobulin with an absence of circulating B lymphocytes. Evidence: PCS. Frequency: 3/3. (PMID:36917008)
These phenotypes are associated with the disease immunodeficiency 131 (OMIM:621097).