Purpose
We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8‐Def) in a tertiary care center for children.
Methods
Retrospective chart review ...of patients' clinical, immunological, and genetic characteristics with DOCK8‐Def. Genetic analysis was performed with targeted‐ or whole‐exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan–Meier method.
Results
We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1–54 months). The median follow‐up time was 53.4 months (4.8–118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum‐driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis.
Conclusion
DOCK8‐Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI‐associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8‐Def. Therefore, an early diagnosis of DOCK8‐Def is essential to facilitate an adequate treatment such as HSCT.
Afebrile Kawasaki disease is not a benign form of the disease Yamazaki‐Nakashimada, Marco; Venegas‐Montoya, Edna; Espinosa‐Navarro, Melissa ...
Pediatrics international,
October 2017, 2017-10-00, 20171001, Letnik:
59, Številka:
10
Journal Article
Mutations in the genes coding for cytokines, receptors, second messengers, and transcription factors of interferon gamma (IFN-γ) immunity cause Mendelian susceptibility to mycobacterial disease ...(MSMD). We report the case of a 7-year-old male patient with partial dominant (PD) IFN-γ receptor 1 deficiency who had suffered from multifocal osteomyelitis attributable to bacille Calmette-Guérin vaccination since the age of 18 months. He developed hemophagocytic lymphohistiocytosis (HLH), a hyper-inflammatory complication, and died with multiorgan dysfunction, despite having been diagnosed and treated relatively early. Patients with PD IFN-γR1 deficiency usually have good prognosis and might respond to human recombinant subcutaneous IFN-γ. Several monogenic congenital defects have been linked to HLH, a catastrophic "cytokine storm" that is usually ascribed to lymphocyte dysfunction and thought to be triggered by interferon gamma. This is the sixth patient with both MSMD and HLH of whom we are aware. The fact that patients with macrophages that cannot respond to IFN-γ still develop HLH, bring these assumptions into question.
is a multiflagellated protozoon which parasitizes the gut of termites and cockroaches. Although L.
infection is rare, it can affect lung, maxillary sinuses and genitourinary tract. The presentation ...of bronchopulmonary lophomonas includes nonspecific symptoms such as fever, cough and dyspnea. Diagnosis is based on identification of living protozoan forms in fresh samples from respiratory secretions (bronchoalveolar lavage). We report the case of a 2-year-old male with a history of severe combined immunodeficiency (T-, B-, NK-), post-hematopoietic stem cell transplant and full immune reconstitution 12 months following a successful transplant who thereafter presented lophomonas.
Autosomal recessive (AR) DOCK8 deficiency is a well-known actinopathy, a combined primary immune deficiency with impaired actin polymerization that results in altered cell mobility and immune ...synapse. DOCK8-deficient patients present early in life with eczema, viral cutaneous infections, chronic mucocutaneous candidiasis, bacterial pneumonia, and abscesses, together with eosinophilia, thrombocytosis, lymphopenia, and variable dysgammaglobulinemia that usually includes Hyper-IgE. In fact, before its genetic etiology was known, patients were described as having a form of Hyper-IgE syndrome, a name now deprecated in favor of genetic defects. We describe a school-age male patient with a clinical picture suggestive of DOCK8 deficiency, except for high serum IgE or a family history: early onset, failure to thrive, eczema, warts, condyloma, bronchiolitis, pneumonia, recurrent otitis media, bronchiectasis, candidiasis, leukocytosis, eosinophilia, high IgA, low IgG, and low CD4+ T cells. We were able to confirm the diagnosis through protein expression and whole-exome sequencing. We review the clinical, laboratory, and genetic features of 200 DOCK8-deficient patients; at least 4 other patients have had no elevated IgE, and about 40% do not have Hyper-IgE (above 1,000 IU/mL). Despite this, the constellation of signs, symptoms, and findings allow the suspicion of DOCK8 deficiency and other actinopathies.
Kawasaki disease (KD) is an acute vasculitis of small and medium vessels; whereas systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Their presentation is varied and not ...always straightforward, leading to misdiagnosis. There have been case reports of lupus onset mimicking KD and KD presenting as lupus-like. Coexistence of both diseases is also possible.
We present three adolescents, one with fever, rash, arthritis, nephritis, lymphopenia, and coronary aneurysms, a second patient with rash, fever, aseptic meningitis, and seizures, and a third patient with fever, rash, and pleural effusion.
The first patient was finally diagnosed with SLE and KD, the second patient initially diagnosed as KD but eventually SLE and the third patient was diagnosed at onset as lupus but finally diagnosed as KD.
The first patient was treated with IVIG, corticosteroids, aspirin, coumadin and mycophenolate mofetil. The second patient was treated with IVIG, corticosteroids and methotrexate and the third patient with IVIG, aspirin and corticosteroids.
Both diseases may mimic each other's clinical presentation. KD in adolescence presents with atypical signs, incomplete presentation, and develop coronary complications more commonly. An adolescent with fever and rash should include KD and SLE in the differential diagnosis.
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated
Mycobacterium ...bovis
-Bacillus Calmette–Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by
Salmonella
, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in
IL12RB1
(
n
= 13),
IFNGR1
(
n
= 3), and
IFNGR2
(
n
= 1) genes. Interleukin-12Rβ1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.
Mutations in recombinase activating genes 1 and 2 (
RAG1/2
) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen ...receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS). A group of previously unrecognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here, we present six patients from unrelated families with missense variants in
RAG1
or
RAG2
. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two variants that had not been associated with immunodeficiency. This study represents the first case series of RAG1- or RAG2-deficient patients from Mexico and Latin America.
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