CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis.

BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients' cells, which we confirmed by means of exogenous induction of expression of CD55. RESULTS: We identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients' T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation. CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Effects of Zinc Sulfate Supplementation in Treatment of Iron Defi ciency Anemia.

OBJECTIVE: In this study, we aimed to compare the effect(s) of zinc sulphate on growth and serum iron variables when it is given with ferrous sulphate in iron deficiency anemia (IDA). MATERIALS AND METHODS: Patients (n=79) were randomly divided into two groups. In one group (n=40) 4 mg/kg/d ferrous sulfate was given orally. In the other group (n=39), in addition to ferrous sulfate, 5 mg/d oral zinc sulfate was given. RESULTS: Compared to the initial values statistically significant increase in mean height, weight, and head circumference has been observed in both groups after 3 months. However, there was no statistical difference between two groups concerning mean height, weight, and head circumference at the beginning (83.43±11.3 cm vs 84.62±12.77 cm; 12.36±3.08 kg vs 12.72±3.87 kg; 47.33±2.15 cm vs 47.26±2.73 cm, respectively), at the first month, (84.82±10.97 vs 85.97±12.28; 12.78±3.09 vs 13.09±3.87; 47.76±2.10 vs 47.61±2.67, respectively), and at the third month, (86.4±11.12 vs 87.69±12.13; 12.9±3.06 vs 13.35±3.81; 48.22±1.89 vs 48.07±2.45, respectively). There were no statistical differences between mean hematological parameters of the groups at the beginning, at the first month, and at the third month, either (mean hb of Group 1: 8.78±1.12 g/dL; 11.27±1.09 g/ dL; 12.05±1.00 g/dL respectively and of Group 2: 9.10±1.07 g/dL; 11.12±0.85 g/dL; 11.80±0.79 g/dL, respectively). Mean ferritin and zinc values of the groups were statistically insignificant at the beginning (Mean ferritin: 4.96±4.03 µg/dL vs 4.52±2.94 µg/dL, zinc: 88.64±15.35 ng/mL vs 86.84±17.34 ng/mL). Their increase was statistically significant at the third month (mean ferritin: 15.91±9.57 µg/dL vs 15.25±10.47 µg/dL; zinc: 88.02±15.10 ng/mL vs 95.25±16.55 ng/mL). CONCLUSION: In our study neither positive nor negative effect of zinc administration on IDA treatment was demonstrated. Therefore, in the treatment of IDA zinc together with iron should be used at different times if there is coexistent zinc deficiency. CONFLICT OF INTEREST: None declared.

Low serum lipocalin levels in patients with iron deficiency anemia.

In the recent literature, there are studies on the relationship between anemia and lipocalin, but there is no study regarding the relationship between lipocalin and iron deficiency anemia (IDA) up to date. In this study, we aimed to observe lipocalin levels at admission, and after iron therapy in children with IDA. We also compared our findings to those in healthy children. Sixty-one children admitted in our outpatient clinic were included in the study. Thirty of these children had IDA (study group) and the rest were healthy (control group). Thirty patients, meeting the IDA criteria, received oral ferrous sulfate of 4 mg/kg/d. As soon as the hemoglobin value reached >11 g/dL, half dose of oral ferrous sulfate therapy was continued for another month. Serum lipocalin levels before and after iron therapies were compared. Hematologic parameters and serum lipocalin levels were also compared between the 2 groups. Mean values of serum lipocalin were 31.01±14.46 and 74.77 ng/dL in patients with IDA at admission and at third month of therapy, respectively (P<0.0001). The same figure was 57.35±39.51 ng/dL in the control group. Before treatment, mean values of lipocalin levels in patients with IDA was significantly lower than the control group (P=0.001); however, such a difference was not detected after 3 months of therapy (P=0.102). We suggest that decreased serum lipocalin levels in our patients during iron insufficiency were caused by iron deficiency rather than anemia.

Acute massive myelofibrosis with acute lymphoblastic leukemia.

Acute myelofibrosis is characterized by pancytopenia of sudden onset, megakaryocytic hyperplasia, extensive bone marrow fibrosis, and the absence of organomegaly. Acute myelofibrosis in patients with acute lymphoblastic leukemia is extremely rare. We report a 4-year-old boy who was diagnosed as having acute massive myelofibrosis and acute lymphoblastic leukemia. Performing bone marrow aspiration in this patient was difficult (a "dry tap"), and the diagnosis was established by means of a bone marrow biopsy and immunohistopathologic analysis. The prognostic significance of acute myelofibrosis in patients with acute lymphoblastic leukemia is not clear.