RESUMEN
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, potentially fatal autosomal-recessive immunodeficiency, and STXBP2 mutations have been associated with FHL type 5 (FHL-5). Here, we report a case of a 2-year-old boy who presented with recurrent fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and hypofibrinogenemia since 4 months of age. His genetic analysis revealed a compound heterozygosity of the STXBP2 gene with a described pathogenic mutation, c.1247-1G>C (splicing acceptor site), harbored by his father and a likely pathogenic variant of uncertain significance (VUS), c.704G>A (p.Arg235Gln), harbored by his mother. He was diagnosed as compound heterozygous for FHL-5 and was treated with the HLH-2004 protocol. Since treatment, this patient has been in remission, and he is being evaluated for a hematopoietic stem cell transplantation (HSCT).
RESUMEN
OBJECTIVE: The objective of this study is to investigate the occurrence of gastrointestinal (GI) and extraintestinal symptoms in children and adolescents with type 1 diabetes mellitus (DM1) and Down syndrome (DS) and their association with specific antibodies and histopathology of celiac disease (CelD), representing its clinical forms in the iceberg. MATERIAL AND METHODS: Cross-sectional study (November 2009-December 2012) conducted at an outpatient care facility in Northeast Brazil including patients [DM1 (n = 111); DS (n = 77)] aged 10 months-18 years old. Measurement of anti-endomysial (EmA) and anti-tissue transglutaminase (anti-tTG) IgA antibodies was performed, as was that of anti-tTG-IgG in the cases with low serum IgA. The patients with antibody positivity were subjected to small intestine biopsy. RESULTS: GI symptoms occurred in 53.7% of the sample, extraintestinal symptoms in 4.3%, and antibody positivity in 28.2% (n = 53). Of those who underwent biopsy (n = 40), histopathological findings of CelD were found in 37.5% [DM1 = 5/111 (4.5%), DS = 10/77 (13.0%)]. GI symptoms were associated with antibody positivity, but not with the histopathology. The GI (32.5%), silent (5.0%), and potential (62.5%) forms of disease were detected. CONCLUSIONS: The prevalence of GI symptoms was high in groups DM1 and DS, and the occurrence of such symptoms was associated with antibody positivity. The lack of association between the symptoms and histopatholological findings points to the inconsistency of the former as indicators of CelD. Although the GI form predominated among the cases with active CelD, its contribution to the celiac iceberg was smaller compared with the potential form, which determined the large and submerged base of the iceberg representing the high-risk groups investigated.