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A 7-year-old child of Turkish origin presented with headache and vomiting in the context of prolonged fever of unknown source. At examination, oral candidiasis and chronic onychomycosis were noted. A Candida meningoencephalitis was diagnosed and intravenous Amphotericin B liposomal was given during 6 months relayed by oral Fluconazole after regression of CNS lesions was observed on MRI. A complete immune evaluation was performed, and genetic analysis detected homozygous CARD9 mutation. CARD9 deficiency have been associated with invasive candidiasis in otherwise healthy patients. Culture of the cerebrospinal fluid grew for multisensitive Candida albicans. Brain magnetic resonance (MRI) showed the presence of focal lesions in the left caudate nucleus and in the right cerebellar hemisphere. Medullar MRI showed diffuse meningeal nodular lesions. Treatment with intravenous amphotericin B liposomal was given during 6 months relayed by oral fluconazole after regression of CNS lesions was observed on MRI. A complete immune evaluation was performed and genetic analysis detected a homozygous CARD9 mutation. CARD9 deficiency have been associated with invasive candidiasis in otherwise healthy patients.

Invasive infections of the central nervous system or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningo-encephalitis and/or colitis caused by Candida remain unexplained. We studied five previously healthy children and adults with unexplained invasive disease of the central nervous system, or the digestive tract, or both, caused by Candida spp. The patients were aged 39, 7, 17 37, and 26 years at the time of infection and were unrelated but each born to consanguineous parents of Turkish (two patients), Iranian, Moroccan or Pakistani origin. Meningo-encephalitis was isolated in three patients, associated with colitis in a fourth patient, and the fifth patient suffered from isolated colitis. Inherited CARD9 deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida, Trichophyton, Phialophora, and Exophiala, including meningo-encephalitis, but not colitis, caused by Candida and Exophiala. We therefore sequenced CARD9 in the five patients. All were found to be homozygous for rare and deleterious mutant CARD9 alleles: R70W and Q289* for the three patients with isolated C. albicans meningo-encephalitis, R35Q for the patient with meningo-encephalitis and colitis caused by C. glabrata, and Q295* for the patient with C. albicans colitis. Regardless of their levels of mutant CARD9 protein, the patients’ monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed C. albicans, Saccharomyces cerevisiae and Exophiala dermatitidis). Invasive infections of the CNS or digestive tract caused by Candida in previously healthy children and even adults may be caused by inherited CARD9 deficiency.

The authors describe a 12-year-old girl with late-onset clinical symptoms due to severe protein C deficiency. Protein C gene analysis showed double heterozygosity for two distinct mutations, associated with type I protein C deficiency. Her parents and only brother were also evaluated. Coumarin-induced skin necrosis was a recurrent feature during oral anticoagulation therapy, forcing her physicians to treat her with nadroparin (Fraxiparin) for only a few months., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Since 1988, 24 children have undergone haematopoietic stem cell transplantation (HSCT) for severe sickle cell disease (SCD) in our unit, 13 being grafted after having been exposed to hydroxyurea (HU) to control SCD-related complications. Different pre-transplant conditioning regimens were given over time: Bu14/Cy200 in six patients (group 1), Bu16/Cy200/antithymocyte globulin (ATG) in five (group 2) and Bu16/Cy200/ATG with HU prior to HSCT in 13 (group 3). The aim of this study is to compare the outcome after HSCT of these groups of patients, which differ according to pre-transplant drug exposure. Overall, 20 of the 24 transplanted children had stable engraftment and have remained free of SCD-related symptoms after HSCT; 19 of them are currently alive and cured of SCD. In group 1 (HU-, ATG-), we observed one unexplainable late death, one absent engraftment, one late rejection and one mixed stable chimerism. In group 2 (HU-, ATG+), we observed the absence of engraftment in two patients and one early rejection. In group 3 (HU+, ATG+), we observed no cases of either absent engraftment, mixed stable chimerism or late rejection. In our experience, pre-transplant treatment with HU seems to be associated with a lower incidence of rejection/absent engraftment in severe SCD patients. These results need to be confirmed with a larger number of patients., Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published