sirolimus and Cryptosporidiosis

Activated phosphoinositide 3-kinase δ syndrome (APDS), a recently described primary immunodeficiency,is caused by autosomal dominant mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD) gene encoding the p110δ catalytic subunit of PI3Kδ (APDS1) or the PIK3R1 gene that encodes the p85α regulatory subunit of PI3Kδ (APDS2). Gain-of-function mutation of PIK3CD in APDS1 leads to p110δ hyperactivity, with the result of the hyperphosphorylation of downstream mediators of Akt and mammalian target of rapamycin that cause a series of clinical symptoms. Few cases with APDS were reported in Asia.. We report a 6-year-old patient with a recurrent respiratory infection, cryptosporidium enteritis, lymphoproliferation, high serum immunoglobulin-M level, anemia, and inverted CD4+/CD8+ ratio. The whole exome sequencing confirmed a heterozygous missense mutation c.3061G>A（p.E1021K）in patient and her mother. Her mutant gene is inherited from her mother, but her mother has not any clinical symptoms.. Activated phosphoinositide 3-kinase δ syndrome.. The patient was received immunoglobulin (Ig) replacement therapy, antibiotics, and rapamycin treatment. Through effectively controlling infection and optimal timing of transplantation by adjusting the conditioning regimen, haploidentical Hematopoietic Stem Cell Transplantation(haplo-HSCT) from her brother was successfully performed.. The patient is in good condiion with a good quality of life after 20 months of follow-up.. We reported a rare APDS1 case with PIK3CD E1021K gene mutation, Successfully treated with haplo-HSCT. This case provided a reference for treating APDS with haplo-HSCT.

Topics: Child; Class I Phosphatidylinositol 3-Kinases; Cryptosporidiosis; Cryptosporidium; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Male; Mutation; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Primary Immunodeficiency Diseases; Quality of Life; Sirolimus

Diarrhoea in transplantation may be secondary to infectious agents and immunosuppressive drugs. The use of combined immunosuppressive drugs increases the incidence of infectious diarrhoea. We retrospectively collected all diarrhoea episodes during a 3-year period in 199 pediatric renal transplant recipients, including 47 patients receiving a kidney transplant during this period. We diagnosed 64 diarrhoea episodes (32% of the patients, 10.7% per year). Fourteen diarrhoea episodes could be attributed to the immunosuppressive treatment, and 12 remained without diagnosis. Nineteen patients (<10%) receiving mycophenolic acid (MPA) developed diarrhoea, 14 of whom had episodes attributable to the immunosuppressive treatment. Reducing the MPA dose or switching to another immunosuppressant did not induce graft rejection, if at all, for at least 6 months. Thirty-eight diarrhoea episodes were caused by infectious agents: viruses in 16 patients, bacterial agents in ten patients, Candida albicans in four cases and parasitic agents in eight cases (Giardia lambdia in one patient and Cryptosporidium in seven patients). In our cohort, Cryptosporidium was responsible for 18% of the infectious diarrhoea and 11% of all causes of diarrhoea, and it affected 3.5% of the newly transplanted patients during the 3-year study period. The clinical presentation of the disease was profuse and persistent diarrhoea with acute renal failure in all patients. We propose that oocysts be screened for in the stool during the early stages of tests for determining the origin of infectious diarrhoea. Disease treatment requires early specific treatment (nitazoxanide) for extended periods of time in conjunction with supportive rehydration.

Topics: Adolescent; Antiparasitic Agents; Biopsy; Child; Cohort Studies; Cryptosporidiosis; Diarrhea; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Mycophenolic Acid; Nitro Compounds; Prednisone; Sirolimus; Tacrolimus; Thiazoles; Time Factors; Transplantation, Homologous; Treatment Outcome