Therapeutic options for CTLA-4 insufficiency.

BACKGROUND: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. OBJECTIVE: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. METHODS: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. RESULTS: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. CONCLUSION: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.

Demyelinating neuropathy in a 6-year-old girl with autism spectrum disorder.

Herein we report the case of a 6-year-old girl with autism spectrum disorder (ASD) and weakness in the distal portion of the right upper limb. Although difficult to perform, nerve conduction studies indicated demyelinating neuropathy. Magnetic resonance imaging (MRI) showed swelling a nd high-intensity signals in the right brachial plexus and cervical spinal roots. The symptoms recovered after a single course of i.v. immunoglobulin. Electrophysiological indices and MRI findings also improved after treatment. This case demonstrates the utility of neuroimaging in addition to electrophysiological assessments for the diagnosis of demyelinating neuropathy, particularly in young patients with ASD.

Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Complications of percutaneously inserted central venous catheters in Japanese neonates.

BACKGROUND: To determine institutional policies concerning percutaneously inserted central venous catheter (PICC) utilization and also frequencies of complications such as pericardial effusion (PCE), cardiac tamponade (CT), pleural effusion, ascites, venous thrombosis, and catheter removal difficulties. METHODS: Nationwide postal questionnaire survey was carried out that included institutional policies on PICC and numbers of complications recorded from January 1999 to December 2003. RESULTS: A total of 98 replies were received from 193 neonatal intensive care units (NICU) in Japan. As a catheter tip location, positions outside of the heart were highly preferred, while only 9% accepted a right atrial position. Twenty-eight cases of PCE or CT were reported, representing an estimated frequency of 0.07-0.11% of PICC insertions. Pleural effusion/ascites and removal difficulties (36 and 35 cases, respectively) were encountered in approximately 0.09-0.14% of insertions. CONCLUSIONS: Frequency of PCE/CT appeared comparable to previously reported occurrences. Also, pleural effusion/ascites and removal difficulty appeared to be rare complications.