Background : Gaucher disease (GD) is an autosomal recessive disorder produced by mutations in the glucocerebrosidase gene (GBA), causing storage of glucosylceramide in reticuloendothelial cells in multiple organs. Traditionally, the prediction of the phenotype based on the genotype has been reported to be limited. Subjects and Methods : We investigated the correlation between the enzymatic residual activity (ERA) and the phenotype at diagnosis of the disease in 45 GD Spanish patients (44 with type I and 1 with type III GD). The genotype involved two of the following previously expressed proteins: c.517A > C (T134P) , 1%; c.721G > A (G202R) , 17%; c.1090G > T (G325W) , 13.9%; c.1208G > A (S364N) , 4.1%; c.1226A > G (N370S) , 17.8%; c.1246G > A (G377S) , 17.6%; c.1289C > T (P391L) , 8.5%; c.1448T > C (L444P) , 3%; and c.1504C > T (R463C) , 24.5%. Recombinant alleles, deletion of 55 bp in exon 9 and 84GG mutation were considered as mutations with no residual enzymatic activity. Results : The ERA showed a statistically significant correlation with chitotriosidase ( P < 0.001), age ( P < 0.001), spleen size ( P < 0.001), ‘Zimran’s Severity Score Index’ ( P < 0.01) and the ‘Gaucher Disease Severity Score Index—Type I’ ( P < 0.0001) at diagnosis of the disorder. Previous to any medical intervention, a comparison between the ERA and bone involvement, demonstrated a statistically significant relationship ( P < 0.01) between the two variables. Conclusions : This study data allowed us to define a new criterion for prognostic assessment of the disease at diagnosis, called Protein Severity Index, which expresses the theoretical severity of the genotype presented by patients, according to the corresponding ERA.

Managing the multisystemic symptoms of type I Gaucher Disease (GD) requires a multidisciplinary team approach that includes disease-specific treatments, as well as supportive care. This involves a range of medical specialists, general practitioners, supportive care providers, and patients. Phenotype classification and the setting of treatment goals are important for optimizing the management of type I GD, and for providing personalized care. The ability to classify disease severity using validated measurement tools allows the standardization of patient monitoring, and the measurement of disease progression and treatment response. Defining treatment goals is useful to provide a benchmark for assessing treatment response and managing the expectations of patients and their families. Although treatment goals will vary depending on disease severity, they include the stabilization, improvement or reversal (if possible) of clinical manifestations. Enzyme replacement therapy (ERT) is the standard care for patients with type I GD, but a novel substrate reduction therapy (SRT), Eliglustat, has demonstrated safety and efficacy in selected patients. To ensure that treatment goals are being achieved, regular and comprehensive follow up are necessary.

Neurofibromatosis type 1 (NF1) is one of the central nervous system’s most common autosomal dominant conditions. The diagnosis is based on the clinical diagnostic criteria and/or a molecularly confirmed mutation in the NF1 gene. This study investigated the possibility of substantiating choroidal nodules as a diagnostic criterion for the disease, including patients affected with and without high myopia. A cross-sectional study was carried out in 60 eyes of 30 adult patients diagnosed with NF1. A total of 30 healthy individuals of equivalent age and sex served as control. The Spectralis HRA+OCT MultiColor (Heidelberg Engineering GmbH, Heidelberg, Germany) evaluated the presence of choroidal abnormalities with near-infrared reflectance imaging. Secondly, the presence of iridian Lisch nodules was evaluated by slit lamp examination. Near-infrared reflectance imaging showed the presence of choroidal hyperreflective nodules in 83% of the patients diagnosed with NF1, while these choroidal abnormalities were not observed in any control subject. The patients diagnosed with NF1 associated with high myopia were the only ones who did not present the characteristic choroidal disorders. Therefore, when excluding patients diagnosed with high myopia, choroidal nodules were more frequent than Lisch nodules in a statistically significant proportion. Hyperreflective nodules detected by near-infrared reflectance imaging are as regular as Lisch nodules or even significantly more frequent when excluding high myope patients. Our observation of the mutual exclusion of choroidal hyperreflective nodules and high myopia in the NF1 patients seems a novel and interesting remark.