Garrahan Hospital

Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare metabolic encephalopathy caused by pathogenic SLC2A1 variants. Ketogenic dietary therapy (KDT) is the mainstay of treatment. In Latin America, Glut1DS remains underdiagnosed due to limited awareness and restricted access to genetic testing. This study describes the clinical and genetic features, management, and response to KDT in an Argentine cohort. A retrospective multicenter study was conducted including patients with a clinical and/or genetic diagnosis of Glut1DS. Clinical data, seizure types, neurodevelopmental features, treatment response, and KDT characteristics were collected from medical records using a standardized form. Genetic confirmation was obtained by SLC2A1 sequencing. Descriptive and comparative analyses were performed. Thirty-nine patients with Glut1DS (64% males) were included. Mean age at evaluation was 13.7 years. Median ages at symptom onset and diagnosis were 6 and 55 months, respectively, with a median diagnostic delay of 49 months. Cognitive impairment was present in two-thirds of patients, and movement disorders in 79%. Epilepsy occurred in 74%. Of 39 patients, all but one received KDT, with MCT oil in 64%. Thirty patients remained on KDT, achieving seizure freedom in 86% and >50% reduction in four others. Improvements were reported in motor coordination (38%), cognition and attention (10%), energy (10%), and behavior (8%). No major adverse effects were reported. This first national report underscores the clinical diversity of Glut1DS in Argentina and a positive trend toward earlier KDT initiation. Strengthening early diagnosis, systematic follow-up, and equitable access to therapy remains essential.

Invasive fungal infections, especially aspergillosis, severely affect immunocompromised patients. The use of azoles, particularly voriconazole, has been considered an effective antifungal therapy for the treatment of these infections and prevention. However, cases of peripheral neuropathy have been reported in patients treated with this drug. We present two clinical cases of patients with immunocompromise (acute myeloblastic leukemia and primary immunodeficiency) who, during treatment with voriconazole, developed peripheral sensory motor axonal polyneuropathy, which completely resolved after discontinuation of the medication. Given the rapid resolution of the clinical manifestations after discontinuation of the drug, we consider it essential to keep this neurotoxicity in mind as a differential diagnosis in children exposed to multiple medications.

Model-informed precision dosing of tacrolimus is crucial to minimize toxicity and prevent graft-vs.-host disease in children undergoing haematopoietic stem cell transplantation (HSCT). Therefore, we developed a population pharmacokinetic model of tacrolimus oral suspension in paediatric HSCT patients that could be used for routine care. Sixteen children receiving continuous intravenous (IV) tacrolimus who were switched to an oral suspension prepared at the hospital pharmacy were included. A total of 339 whole-blood samples were collected and quantified by immunoassay: 260 during IV administration and 79 from 12-h pharmacokinetic profiles (at 0, 20 min, 1, 3 and 12 h) after oral administration. Data analysis was performed using a nonlinear mixed-effects approach with Monolix considering demographic, clinical and pharmacological factors as potential covariates influencing tacrolimus pharmacokinetics. A 1-compartment model with linear elimination adequately described tacrolimus pharmacokinetics. The typical estimated values (% relative standard error) for clearance, volume of distribution and absolute bioavailability were 1.5L/h (9.5%), 42.3L (17.5%) and 40.0% (14.8%), respectively. A mean lag time of 0.3h best characterized the delay in the absorption phase. Body weight was significantly associated with clearance, volume of distribution and bioavailability. A population pharmacokinetic model was developed to describe the pharmacokinetics of tacrolimus during continuous IV infusion or oral suspension administration in paediatric HSCT patients, which may be used for individualized dose adjustment. The mean bioavailability of the oral suspension was 40%, suggesting a dose conversion factor of 2.5 from IV to oral suspension therapy in our clinical setting.

Se presenta el caso de un niño de 18 meses con múltiples fracturas secundarias a un trauma no accidental, al ser arrastrado por las escaleras, por su cuidadora. Se define el protocolo radiológico utilizado en nuestra institución para los casos de trauma no accidental, su diagnóstico y el tratamiento ortopédico y social.

Introduction CD40 ligand (CD40L) deficiency is a rare X-linked primary immunodeficiency. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment. To date, regional studies have focused on reporting the clinical characteristics of this disease rather than transplant outcomes. This study aims to characterize pediatric patients with CD40L deficiency who have undergone HSCT in centers from Chile, Colombia, Brazil, Mexico, and Argentina. Objectives include describing clinical features, evaluating survival, identifying mortality-associated factors, and reporting major posttransplant complications. Methods We retrospectively reviewed pediatric patients with CD40L deficiency who underwent HSCT between January 2002 and December 2024. We analyzed clinical characteristics, survival outcomes, and complications. Descriptive statistics were used, and overall survival was estimated using Kaplan–Meier analysis. During this period, 27 patients with CD40L deficiency were included in the study. For one patient, data from a second HSCT were also collected. Results Twenty-seven pediatric patients with CD40L deficiency underwent HSCT, with a median age at transplant of 6 years (range 1–18). A confirmed genetic diagnosis was present in 96% of cases, and 12 patients (44%) had a positive family history. Pretransplant complications included pneumonia in 14 patients (52%), gastrointestinal symptoms in 15 patients (56%), neutropenia (26%), and cholangitis (11%). Infectious history included Pneumocystis jirovecii (22%), CMV (7%), Cryptosporidium (15%), and Candida (26%). Intravenous immunoglobulin (IVIG) supplementation was administered before transplant in 96% of patients, and 67% continued IVIG posttransplant. Cotrimoxazole prophylaxis was given prior to HSCT in 93% of cases. Unrelated donors were used in 70% of patients, and most received conditioning with treosulfan/busulfan plus fludarabine. Graft versus host disease (GVHD) prophylaxis included antithymocyte globulin (ATG) in 59% of patients and calcineurin inhibitors in 96%. Engraftment was achieved in 93% of patients, and 3 required a second transplant. Acute GVHD grade III–IV occurred in 30%, and chronic GVHD in 26%. CMV occurred in 10 patients, with one fatal case. A total of four deaths were reported—three were HSCT-related. Overall survival was 83.6% at 1 year, 78.7% at 3 years, and 78.7% at 5 years. Conclusions This multicenter retrospective study analyzed pediatric patients with CD40L deficiency who underwent HSCT. The cohort showed favorable 5-year overall survival. A genetic diagnosis was confirmed in 96% of patients, while one-third had a positive family history. Most patients experienced significant complications prior to transplant, and HSCT was delayed by a median of 5.5 years. Prophylaxis included IVIG in 96% of cases and cotrimoxazole in 93%. Most transplants used matched unrelated donors (MUD), with busulfan/fludarabine-based conditioning regimens. Conditioning approaches varied by center. Serotherapy (mainly ATG) was used in 70% of patients. Engraftment was successful in 93% of cases. Posttransplant complications were frequent. Acute GVHD occurred in 30% of patients, mostly in severe forms (grade III–IV), while 26% developed chronic GVHD. CMV reactivation was reported in 44%, and graft-related complications (“graft problems”), including secondary graft failure and mixed chimerism, were observed in 26% of cases.