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Background The Gaucher Investigative Therapy Evaluation (GAUCHERITE) is a national clinical cohort of 250 patients aged 5–87 years with Gaucher disease - an ultra-rare genetic disorder. To inform clinical decision-making and improve pathophysiological understanding, we characterized the course of Gaucher disease and explored the influence of costly innovative medication and other interventions. Retrospective and prospective clinical, laboratory and radiological information including molecular analysis of the GBA1 gene and comprising > 2500 variables were collected systematically into a relational database with banking of collated biological samples in a central bioresource. Data for deep phenotyping and life-quality evaluation, including skeletal, visceral, haematological and neurological manifestations were recorded for a median of 17.3 years. Results At baseline, 223 of the 250 patients were classified as type 1 Gaucher disease. Intensive neurological phenotyping in a subgroup of 40 originally considered to have only systemic features, revealed neurological involvement in 18: two had Parkinson disease and 16 patients had other neuronopathic features. This revised the number affected by type 3 Gaucher disease to a total to 43. Skeletal manifestations occurred in most patients in the cohort (131 of 201 specifically reported bone pain). Symptomatic osteonecrosis and fragility fractures occurred respectively in 76 and 37 of all 250 patients and the first osseous events occurred significantly earlier in those with neuronopathic disease. Analysis of the longitudinal real-world data permitted stratification of Gaucher disease on the basis of exposure to advanced therapies and splenectomy. Splenectomy was associated with an increased hazard of fragility fractures, osteonecrosis and orthopaedic surgery; after splenectomy, there were marked gender differences in the risk of fragility fractures over time. Combined with associated surgical procedures, the skeletal manifestations represent a heavy burden of illness, especially in patients formerly unable to access disease-modifying therapies. Conclusion Gaucher disease has been explored during a period of transformation by disease-modifying interventions. With the introduction of advanced therapies, repeated longitudinal measures in this real-world cohort allowed the condition to be stratified into clear clinical endotypes. Our study reveals diverse and changing phenotypic manifestations with neurological, systemic and skeletal disease as inter-related sources of disability. Electronic Supplementary Material The online version of this article contains supplementary material, which is available to authorized users.

Background Immunisation of children is a highly cost-effective public health intervention and fosters health equity for the overall population. The WHO Immunisation Agenda 2030 highlights coverage and equity as one of the strategic priority goals to reach high equitable immunisation coverage at national levels and in all districts. We analysed full immunisation coverage among children aged 12-23 months in Kenya and estimated the inequities in full immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics using data from the 2014 Kenya Demographic and Health Survey. Methods We analysed full immunisation coverage (1-dose BCG, 3-dose DTP-HepB-Hib, 3-dose polio, 1-dose measles, and 3-dose pneumococcal vaccines) of 3,943 children aged 12–23 months. We disaggregated mean coverage by socioeconomic (household wealth, religion, ethnicity), geographic (place of residence, province), maternal (maternal age at birth, maternal education, maternal marital status, maternal household head status), child (sex of child, birth order), and place of birth characteristics. We conducted bivariate and multivariate logistic regression to assess associations between full immunisation coverage and socioeconomic, geographic, maternal, child, and place of birth characteristics. Results Immunisation coverage ranged from 82% [81–84] for the third dose of polio to 97.4% [96.7–98.2] for the first dose of DTP-HepB-Hib, while full immunisation coverage was 68% [66–71] in 2014. After controlling for other background characteristics, children of mothers with primary school education or higher have at least 54% higher odds of being fully immunised compared to children of mothers with no education. Children born in clinical settings have 41% higher odds of being fully immunised compared to children born in home settings. Children in the Coast, Western, Central, and Eastern regions had at least 74% higher odds of being fully immunised compared to children in the North Eastern region, while children in urban areas had 26% lower odds of full immunisation compared to children in rural areas. Children in the middle and richer wealth quintile households were 43–57% more likely to have full immunisation coverage compared to children in the poorest wealth quintile households. Children who were sixth born or higher had 37% lower odds of full immunisation compared to first-born children. Conclusions The inequities in full immunisation adversely affect children of mothers with no education, born in home settings, in regions with limited health infrastructure, living in poorer households, and of higher birth order. Further, the COVID-19 pandemic has disrupted routine and campaign immunisation services in 2020 and enhances the risk of vaccine-preventable disease outbreaks, but it also presents an opportunity to tackle the identified inequities in vaccine uptake as immunisation services are restored to capacity.

Background Neurological forms of Gaucher disease, the inherited disorder of β-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with enzyme replacement therapy, however, molecules which cross the blood–brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of ‘type 3’ Gaucher disease. Methods We undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video-oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups. Results We confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared a GBA1 variant. Conclusions This striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.