Untreated women with Gaucher disease (GD) are at an increased risk of GD-related complications during pregnancy. Enzyme replacement therapy with imiglucerase is effective at improving hematologic, visceral, and bone manifestations of GD, and the Food & Drug Administration prescribing information supports that imiglucerase is not associated with adverse maternal or fetal outcomes when used during pregnancy. This study population included women with GD enrolled in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943) Pregnancy Sub-Registry who were treated with imiglucerase during at least one pregnancy as of October 2023. We describe frequency of pregnancy outcomes, birth outcomes, and maternal and neonatal complications. Imiglucerase exposure was reported in 110 pregnancies in 68 women with GD type 1; 68% of pregnancies were exposed during all three trimesters. Of 104 fetuses with reported data, 92 were live births (88.5%), eight were spontaneous abortions (7.7%), and four were elective/therapeutic terminations (3.8%); no stillbirths (> 20 weeks gestation) were reported. The majority of infants (80 of 85 [94.1%]) were born at term. Among 108 pregnancies with data, maternal pregnancy, labor and delivery, and post-partum complications were reported for 33 (30.6%), 26 (24.1%), and 24 (22.2%) pregnancies, respectively, with anemia, thrombocytopenia, and vaginal bleeding among the most prevalent complications. Among 74 infants with data, neonatal complications were reported for seven infants (9.5%). Most pregnancies to women with GD treated with imiglucerase resulted in live births and healthy infants, with risk of spontaneous abortions similar to that of the general population (12%-18%).

This report describes two cases of severe immune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation (HSCT) who were treated with umbilical cord mesenchymal stem cells (UC-MSCs). Case 1 was a child with severe aplastic anemia who underwent haploidentical bone marrow and peripheral blood HSCT, with a chimerism rate of 99.8% on day +25 and severe immune-mediated thrombocytopenia on day +60. After intravenous immunoglobulin (IVIG) pulse therapy, platelet count increased temporarily but then decreased, while cyclosporine, methylprednisolone, and rituximab had a poor therapeutic effect. Case 2 was a child with Gaucher's disease who underwent unrelated umbilical cord blood HSCT, with a chimerism rate of 96.35% on day +41 and severe immune-mediated thrombocytopenia on day +153. After three sessions of IVIG pulse therapy, the platelet count increased initially but subsequently decreased. Therapies with dexamethasone, prednisone, cyclosporine, and recombinant human thrombopoietin also yielded a poor response. Both children received three sessions of UC-MSCs infusion, and platelet counts increased and were subsequently maintained within the normal range. Case 1 has been followed up for 10 years and remains in disease-free survival. UC-MSCs infusion may be effective for severe immune-mediated thrombocytopenia that is unresponsive to first- and second-line therapies after HSCT and could potentially improve the quality of life and disease-free survival rate. 该文报道了2例应用脐带间充质干细胞（umbilical cord mesenchymal stem cells UC-MSCs）治疗儿童异基因造血干细胞移植（hematopoietic stem cell transplantation, HSCT）后重型免疫介导性血小板减少症（immune-mediated thrombocytopenia, IMTP）的患儿。例1为极重型再生障碍性贫血患儿，行单倍体骨髓+外周血HSCT，+25 d嵌合率达99.8%，+60 d出现重型IMTP，给予静脉注射免疫球蛋白冲击治疗后血小板短暂上升后下降，给予环孢素、甲泼尼龙、利妥昔单抗治疗效果差。例2为戈谢病患儿，行非血缘脐血HSCT，+41 d查嵌合率为96.35%，+153 d出现重型IMTP，先后给予3次静脉注射免疫球蛋白冲击治疗后血小板上升后又下降，给予地塞米松、泼尼松、环孢素及重组人血小板生成素治疗效果差。2例患儿均输注3次UC-MSCs，血小板上升并维持在正常水平。例1已随访10年，无病生存。UC-MSCs治疗对HSCT后一、二线治疗无效的重型IMTP有一定疗效，可提高HSCT后重型IMTP患儿的生活质量及无病生存率。.

Pompe disease (PD), an autosomal recessive lysosomal disorder, results in glycogen accumulation in muscle cells, leading to progressive muscle weakness and respiratory insufficiency. Newborn screening (NBS) has improved outcomes for infantile-onset PD by enabling early diagnosis and intervention with enzyme replacement therapy. NBS also identifies late-onset PD (LOPD) cases, wherein children have a wide clinical spectrum and may remain asymptomatic for years, placing families in uncertainty as "patients-in-waiting." This study explores parental experiences following an LOPD diagnosis through NBS to identify gaps in support systems and improve care delivery. Parents of 42 children diagnosed with LOPD through NBS completed a survey regarding their diagnostic experiences, care access, anxiety, and health care professionals' (HCPs') roles. Survey responses were analyzed using descriptive statistics, thematic analysis, and Kruskal-Wallis tests. Parents valued clear guidance and condition-specific information when receiving NBS results. However, many reported insufficient support and HCP's limited LOPD knowledge. About 70.7% experienced reduced anxiety following the LOPD diagnosis, attributed to increased knowledge, supportive health care teams, and their child's stable health, although uncertainty persisted. Among those who saw an HCP, 71.9% reported positive impacts, including improved understanding and mental health support, although 19% thought counseling or information provided lacked clarity or actionable resources. Timely communication with knowledgeable HCPs and multidisciplinary support can potentially reduce the psychosocial burden on families receiving positive NBS results. Efforts should prioritize creating more resources for HCPs and improving communication to ensure consistent compassionate care.

Background/Objectives: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the GBA1 gene. Type 1 Gaucher disease is characterised by substrate accumulation in the visceral organs, which occurs in combination with acute and chronic neurodegeneration that distinguish type 2 and type 3 GD, respectively. We have previously shown the efficacy of neonatal AAV9 gene therapy for treating type 2 GD and aimed to investigate post-symptomatic administration into a model of type 1 disease. Current murine models of type 1 disease are limited in their recapitulation of early onset phenotypic manifestation and thus we aimed to create a novel model of type 1 in which to test the efficacy of adult gene therapy. Methods: The novel AAV-GD1 model was created through intracerebroventricular injection of AAV9 containing the human GBA1 gene under control of the neuron-specific synapsin promoter (AAV9.hSynI.hGBA1) to the pre-existing acute K14-lnl/lnl model of type 2 GD. Administration of AAV9.hSynI.hGBA1 aimed to restore glucocerebrosidase expression in the brain and extend the lifespan beyond 14 days, allowing the visceral pathology to develop further. The organ pathology was characterised by immunohistochemistry at various time points. Once visceral disease was confirmed, an intravenous injection of AAV9 containing a ubiquitously active CAG promoter driving hGBA1 (AAV9.CAG.hGBA1) was administered to post-symptomatic mice. Animals were aged for 2 and 4 months post-treatment with AAV9.CAG.hGBA1, and immunohistochemistry and enzymatic activity were assessed to investigate therapeutic efficacy. Results: The AAV-GD1 model displayed visceral pathology in the spleen, lung, and liver from 2 months of age. This allowed us to validate the efficacy of adult gene therapy; intravenous administration of AAV9.CAG.hGBA1 transiently ameliorated the lung pathology and rescued the spleen pathology up to 4 months post-administration. Conclusions: The creation of the novel AAV-GD1 model with more aggressive visceral pathology presents a unique opportunity for investigation of new therapies to treat type 1 GD. AAV9.CAG.hGBA1 represents a potential therapeutic option for all forms of Gaucher disease.

Standardised procedures for performing and reporting safety monitoring studies investigating medications use in pregnancy may help improve data quality and the speed of data generation. The objective of this study was to provide recommendations on the statistical analysis and reporting of single-arm pregnancy medication safety studies using primary source datasets. A Delphi consensus-setting protocol was used to acquire agreement on recommendations from experts with extensive knowledge and experience in conducting studies investigating medication safety in pregnancy. A series of recommendations, along with their scientific justifications and examples of how to calculate and describe exposure and outcome incidences, were critiqued and improved through a series of online Delphi review rounds. Agreement to inclusion scoring was assessed using a five-point Likert scale. Recommendations with a median Likert-scale score of at least 4, where ≥ 80% of the expert panel scored the recommendation at level 4 or higher, was used as the threshold for inclusion. The Delphi consensus methodology produced a set of 30 recommendations spread over five themes. These included descriptions of (1) study sample, (2) medication exposure, (3) maternal outcomes, (4) pregnancy and birth outcomes, and (5) fetal and neonatal outcomes. Of the 30 recommendations, 19 were strongly advised while 11 were included for consideration where their implementation may be beneficial for supplementing data communication. Use of the finalised set of recommendations should be encouraged to help standardise published evidence around medication use in pregnancy.