Identification of risk features for complication in Gaucher’s Disease patients: A Machine Learning analysis of the Spanish Registry of Gaucher Disease.

Abstract

Background : Since enzyme replacement therapy for Gaucher disease (MIM#230800) has become available, both awareness of and the natural history of the disease have changed. However, there remain unmet needs such as the identification of patients at risk of developing bone crisis during therapy and late complications such as cancer or parkinsonism. The Spanish Gaucher Disease Registry has worked since 1993 to compile demographic, clinical, genetic, analytical, imaging and follow-up data from more than 400 patients. The aims of this study were to discover correlations between patients’ characteristics at diagnosis and to identify risk features for the development of late complications; for this a machine learning approach involving correlation networks and decision trees analyses was applied. Results : A total of 358 patients, 340 type 1 Gaucher disease and 18 type 3 cases were selected. 18% were splenectomyzed and 39% had advanced bone disease. 81% of cases carried heterozygous genotype. 47% of them were diagnosed before the year 2000. Mean age at diagnosis and therapy were 28 and 31.5 years old (y.o.) respectively. 4% developed monoclonal gammopathy undetermined significance or Parkinson Disease, 6% cancer, and 10% died before this study. Previous splenectomy correlates with the development of skeletal complications and severe bone disease (p=0.005); serum levels of IgA, delayed age at start therapy (>9.5 y.o. since diagnosis) also correlates with severe bone disease at diagnosis and with the incidence of bone crisis during therapy. High IgG (>1750mg/dL) levels and age over 60 y.o. at diagnosis were found to be related with the development of cancer. When modelling the decision tree, patients with a delayed diagnosis and therapy were the most severe and with higher risk of complications. Conclusions : Our work confirms previous observations, highlights the importance of early diagnosis and therapy and identifies new risk features such as high IgA and IgG levels for long-term complications.

Gaucher disease prevalence in 600 patients affected by monoclonal gammopathy of undetermined significance

“…The prevalence of polyclonal gammopathies and monoclonal gammopathy ranged from 25% to 91% and from 0% to 35%, respectively (Table 1). [6][7][8][9][10][11][12][13][14][15][16][17][18] Interestingly. In contrast, some patients were severely affected with massive hepatosplenomegaly, lung involvement, and avascular necrosis of the hip joint, in others, both polyclonal and monoclonal gammopathy were frequently associated with patients older than 50 years with only a mild clinical presentation of Gaucher disease.…”

Early diagnosis of Gaucher disease in Korean patients with unexplained splenomegaly: a multicenter observational study

“…Although the prevalence rate of GD has not yet been evaluated in Asian countries, according to a report from Yoo's group, approximately 60 Korean patients from 50 families have been identified until 2013, demonstrating an enormous gap from the pan-ethnic prevalence of 1 in 40,000-100,000 live births [9,10]. Therefore, determining the prevalence rate of GD will provide important insights into the ethnical and clinical features of GD in a Korean population.…”