ABSTRACT
We report a kindred with autosomal recessive interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency in 3 fourth-degree relatives. A diagnosis of IRAK-4 deficiency should be considered in families with invasive bacterial disease, even if the individuals affected are only distantly related, which falsely suggests multigenic or dominant inheritance with low penetrance.
Subject(s)
Family Health , Genes, Recessive , Immunologic Deficiency Syndromes/genetics , Intracellular Signaling Peptides and Proteins/deficiency , Intracellular Signaling Peptides and Proteins/genetics , Protein Serine-Threonine Kinases/deficiency , Protein Serine-Threonine Kinases/genetics , Child , Child, Preschool , Humans , Immunologic Deficiency Syndromes/microbiology , Infant , Interleukin-1 Receptor-Associated Kinases , Pedigree , Pneumococcal Infections/etiology , Recurrence , Spain , Staphylococcal Infections/etiologyABSTRACT
OBJECTIVES: Mediterranean classic Kaposi sarcoma (KS) of childhood is rare and unexplained. Our objective is to describe the case of a child with complete IFNgammaR1 deficiency and severe mycobacterial disease in whom Kaposi sarcoma (KS) developed. RESULTS: Disseminated mycobacterial infection began at the age of 5 months, and at 11 years of age the child had disseminated KS lesions. The histologic appearance of these lesions was typical, with endothelial and spindle cell proliferation. Human herpesvirus-8 (HHV-8)-associated antigens were detected in situ by immunohistochemistry. HHV-8 DNA of K1 molecular subtype A was amplified from tissue lesions, and HHV-8-specific antibodies were detected in the patient's serum. The child died at 12 years of age of disseminated mycobacterial disease and KS. CONCLUSIONS: This is the first identification of a well-defined primary immunodeficiency in a child with KS. Inherited disorders of IFN-gamma-mediated immunity and severe mycobacterial disease may predispose HHV-8-infected children to KS.
Subject(s)
Herpesviridae Infections/complications , Receptors, Interferon/deficiency , Sarcoma, Kaposi/complications , Skin Neoplasms/complications , Child , Consanguinity , Fatal Outcome , Herpesvirus 8, Human , Humans , Immunologic Deficiency Syndromes/genetics , Male , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium fortuitum , Receptors, Interferon/genetics , Sarcoma, Kaposi/pathology , Sarcoma, Kaposi/virology , Skin Neoplasms/pathology , Skin Neoplasms/virology , Interferon gamma ReceptorABSTRACT
OBJECTIVE: To document the frequency and outcome of endocrine involvement in pediatric-onset Langerhans' cell histiocytosis (LCH), and the association with other types of organ involvement. STUDY DESIGN: This retrospective nationwide multicenter study involved 589 patients with pediatric-onset LCH, 148 of whom had endocrine dysfunction. Median follow-up was 11.6 years. RESULTS: Pituitary dysfunction was present in 145 patients, and 141 had diabetes insipidus (DI). The estimated 10-year risks of pituitary involvement were 24.2% +/- 1.8%. GH deficiency occurred in 61 patients. Median age at onset was 2.8 years for LCH, 3.9 years for DI, and 7.7 years for GH deficiency. The risk of cranial involvement; ear, nose, and throat involvement; pneumothorax; and cholangitis was significantly higher in patients with endocrinopathy. The chronology of episodes did not support a causal link between pituitary involvement and involvement of other organs. Systemic treatment of LCH did not prevent pituitary involvement. The most severe complication was a neurodegenerative syndrome, which affected 4.3% and 10.8% of patients, respectively, 5 and 15 years after initial diagnosis, and appeared to be linked to pituitary involvement. CONCLUSION: Patients who develop endocrine LCH disorders are at a high risk of neurodegenerative LCH and require long-term follow-up.