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Introduction: Access in France to early diagnosis and care for the most severe, but infrequent, Neurodevelopmental Disorders (NDD), autism spectrum disorder and global developmental delay, in children aged 0-7 was improved through measures implemented in 2019. However, there are no such measures for specific learning disorders (SLD), attention, motricity and language disorders (SLDD), despite their annual incidence of between 5 and 8%. Method: We describe the design of a new type of organization and financing of care for SLDD including evaluation procedure, as well as other factors, mainly at the prevention level that will contribute to local and national policy for this frequent health problem. This in response to a national call for projects, commonly called Article 51, targeted innovation in healthcare delivery and funding in the context of medium-term national reform. This provides project stakeholders with the opportunity to set up and implement "bottom-up" projects, mainly using local professionals. A joint initiative by the regional Health Authorities of the Occitanie region, the French Social Security system and a non-profit Association (Occitadys) proposed an experimental new structure of NDD care and funding. Discussion: We here discuss the design of this experiment that aims, over two to three years, to alleviate families' financial burden of care and establish a regional three-tier care system with respect to evaluation, re-education and rehabilitation care. Our approach may benefit SLDD health-care planning, and addresses the questions of prevention, early detection and care-design for families, taking local and socioeconomic disparities into account.
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Importance: Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia due to mutations in the aprataxin gene (APTX) that is characterized by early-onset cerebellar ataxia, oculomotor apraxia, axonal motor neuropathy, and eventual decrease of albumin serum levels. Objectives: To improve the clinical, biomarker, and molecular delineation of AOA1 and provide genotype-phenotype correlations. Design, Setting, and Participants: This retrospective analysis included the clinical, biological (especially regarding biomarkers of the disease), electrophysiologic, imaging, and molecular data of all patients consecutively diagnosed with AOA1 in a single genetics laboratory from January 1, 2002, through December 31, 2014. Data were analyzed from January 1, 2015, through January 31, 2016. Main Outcomes and Measures: The clinical, biological, and molecular spectrum of AOA1 and genotype-phenotype correlations. Results: The diagnosis of AOA1 was confirmed in 80 patients (46 men [58%] and 34 women [42%]; mean [SD] age at onset, 7.7 [7.4] years) from 51 families, including 57 new (with 8 new mutations) and 23 previously described patients. Elevated levels of α-fetoprotein (AFP) were found in 33 patients (41%); hypoalbuminemia, in 50 (63%). Median AFP level was higher in patients with AOA1 (6.0 ng/mL; range, 1.1-17.0 ng/mL) than in patients without ataxia (3.4 ng/mL; range, 0.8-17.2 ng/mL; P < .01). Decreased albumin levels (ρ = -0.532) and elevated AFP levels (ρ = 0.637) were correlated with disease duration. The p.Trp279* mutation, initially reported as restricted to the Portuguese founder haplotype, was discovered in 53 patients with AOA1 (66%) with broad white racial origins. Oculomotor apraxia was found in 49 patients (61%); polyneuropathy, in 74 (93%); and cerebellar atrophy, in 78 (98%). Oculomotor apraxia correlated with the severity of ataxia and mutation type, being more frequent with deletion or truncating mutations (83%) than with presence of at least 1 missense variant (17%; P < .01). Mean (SD) age at onset was higher for patients with at least 1 missense mutation (17.7 [11.4] vs 5.2 [2.6] years; P < .001). Conclusions and Relevance: The AFP level, slightly elevated in a substantial fraction of patients, may constitute a new biomarker for AOA1. Oculomotor apraxia may be an optional finding in AOA1 and correlates with more severe disease. The p.Trp279* mutation is the most frequent APTX mutation in the white population. APTX missense mutations may be associated with a milder phenotype.
