dRTA and hemolytic anemia: first detailed description of SLC4A1 A858D mutation in homozygous state.

Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride-bicarbonate) exchanger 1 may result in familial distal renal tubular acidosis (dRTA) in association with membrane defect hemolytic anemia. Seven children presenting with hyperchloremic normal anion gap metabolic acidosis, failure to thrive, and compensated hemolytic anemia were studied. Analysis of red cell AE1/Band 3 surface expression by Eosin 5'-maleimide (E5M) was performed in patients and their family members using flow cytometry. Genetic studies showed that all patients carried a common SLC4A1 mutation, c.2573C>A; p.Ala858Asp in exon 19, found as homozygous (A858D/A858D) mutation in the patients and heterozygous (A858D/N) in the parents. Analysis by flowcytometry revealed a single uniform fluorescence peak, with the mean channel fluorescence (MCF) markedly reduced in cases with homozygous mutation, along with a left shift of fluorescence signal but was only mildly reduced in the heterozygous state. Red cell morphology showed striking acanthocytosis in the homozygous state [patients] and only a mild acanthocytosis in heterozygous state [parents]. In conclusion, this is the first description of a series of homozygous cases with the A858D mutation. The E5M flowcytometry test is specific for reduction in the Band 3 membrane protein and was useful in conjunction with a careful morphological examination of peripheral blood smears in our patient cohort.

A de-escalation protocol for febrile neutropenia cases and its impact on carbapenem resistance: A retrospective, quasi-experimental single-center study.

Our objective was to evaluate the impact of using an imipenem de-escalation protocol for empiric febrile neutropenia on the development of carbapenem resistance. A pre-post intervention design was used. The intervention was adopting the imipenem de-escalation approach, which began on January 1, 2012. A retrospective chart review of cases of febrile neutropenia bacteremia was performed one year before and one year after the intervention. We compared the development of carbapenem resistance between the two study periods. Seventy-five episodes of febrile neutropenia bacteremia were included in the study. They had similar demographics, clinical features and outcomes. There were 78 and 12 pathogens in the primary and follow-up blood cultures, respectively. Approximately 61% and 66% of the primary and follow-up blood cultures, respectively, were gram-negative bacteria with similar carbapenem resistance profiles in the two study periods. In our study population, 57% of the gram-negative bacteria were ESBL pathogens. The resistance of the gram-negative bacteria to piperacillin/tazobactam (72% versus 53%, p=0.161), imipenem (16% versus 11%, p=0.684), and meropenem (8% versus 16%, p=0.638) did not significantly change after our policy change. In conclusion, the use of the carbapenem de-escalation approach for febrile neutropenia in our institution was not associated with an increase in carbepenem resistance. Future prospective multi-center studies are recommended to further confirm the current findings.

Fatal hemophagocytic syndrome as a manifestation of immune reconstitution syndrome in a patient with acquired immunodeficiency syndrome.

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and potentially life-threatening condition characterized by uncontrolled hyper inflammation caused by various inherited or acquired immune deficiencies. We report a case of a 42-year-old man, newly diagnosed with HIV on the basis of a low CD4 T lymphocyte count (17/mm³) and HIV viral load >100,000 copies/mL by polymerase chain reaction tests who was undergoing an anti-retroviral regimen (emitricitabine, tenofovir disoproxil fumarate, ritonavir, and darunavir) and opportunistic infection prophylaxis (clarithromycin and atovaquone). He was concomitantly diagnosed with hemophagocytic syndrome, also known as HLH. He developed increasingly severe pancytopenia while on treatment with anti-retroviral drugs.