From Gaucher disease to Parkinson Disease: a new light on the lysosome

Gaucher disease type 1 is a lysosomal storage disease with hematological and bone involvement and visceromegaly. Until about twenty years ago it was commonly accepted that neurological involvement could only occur in the most severe forms, type 2 and type 3 Gaucher disease. This principle has been questioned since the first series of patients with Parkinson's disease and Gaucher’s disease were described. It was then clearly demonstrated that the GBA1 mutation, which is responsible for Gaucher’s disease, was also responsible for Parkinson's disease. Glucocerebrosidase, which is active in the lysosome and deficient in Gaucher’s disease, is closely correlated with the accumulation and aggregation of synuclein found in Parkinson's disease. Improving knowledge on rare diseases has an impact on the knowledge of more frequent disease. In this work, we highlight some of the most recent discoveries on Gaucher’s disease through the description of new clinical manifestations, the trend to personalized treatment, and the discovery of new complications. Through these different manifestations associated with Gaucher's disease, we show how an ultra-rare disease can help to better understanding of a very common one and can lead to other therapeutics. As a consequence, glucocerebrosidase represents a promising target to develop further disease modifying treatments in Parkinson’s disease

Imiglucerase in the management of Gaucher disease type 1: an evidence-based review of its place in therapy

Gaucher disease is the first lysosomal disease to benefit from enzyme replacement therapy, thus serving as model for numerous other lysosomal diseases. Alglucerase was the first glucocerebrosidase purified from placental extracts, and this was then replaced by imiglucerase - a Chinese hamster ovary cell-derived glucocerebrosidase

Drug-induced hypersensitivity syndrome with lupus manifestations due to mesalazine in a patient with ulcerative colitis

Mesalazine is often used as first-line therapy for ulcerative colitis. Several reports have pointed to systemic adverse reactions associated with this drug. Most have evoked a drug-induced hypersensitivity syndrome, while some have described lupus syndromes but with limited clinical and varied biological features. A 75-year-old man presented with fever, dyspnoea, chest pain, polyarthralgia, and myalgia, following mesalazine introduction. Clinical symptoms and low-titre positive antihistone antibodies disappeared after mesalazine withdrawal without recourse to steroids. Pericardial effusion and 8F-fluorodeoxyglucose uptake on positron emission tomography/CT scan, and glomerular haematuria and proteinuria also disappeared. Cytokine-lymphocyte transformation tests showed a strong sensitisation pattern with interleukin-5 production. This case advances our knowledge of the mechanism of mesalazine-induced adverse effects, namely via drug-induced hypersensitivity with lupus manifestations, which we are the first to report

Type I Gaucher disease with bullous pemphigoid and Parkinson disease: A case report

Gaucher disease (GD) is a rare genetic lysosomal storage disorder inherited in an autosomal recessive pattern. GD is due to the deficiency of a lysosomal enzyme, acid beta-glucosidase (or glucocerebrosidase). Type 1 Gaucher disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen, and liver as well as bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts, and avascular necrosis leading to degenerative arthropathy). The diagnosis is usually made in first decades but is sometimes delayed. Parkinson disease, neoplasia, and immune system abnormalities may be associated with GD1

Nutritional risk at hospital admission is associated with prolonged length of hospital stay in old patients with COVID-19

Background & aims: To investigate the association of nutritional risk at admission with the length of hospital stay (LOS) and mortality in older patients with COVID-19. Methods: Retrospective monocentric study in an acute geriatric hospital. Data were collected after an extensive review of medical records and the nutritional risk was assessed according to the Nutritional Risk Screening (NRS). Univariate and multivariate (adjusted for age, sex and comorbidity burden) Cox proportional-hazard and linear regression models were used to investigate the association with the above-mentioned outcomes. Results: Of a total of 245 patients (86.1 ± 6.4 yrs), 50.6% had a severe nutritional risk with an NRS≥5/7 at admission. Lower BMI, cognitive impairment and swallowing disorders were more prevalent in the patients with a higher NRS. A NRS≥5 was not associated with mortality but prolonged by more than 3 days the LOS among the 173 survivors (β 3.69; 0.71-6.67 95% CI; p = 0.016), with a discharge rate delayed by 1.8 times (HR 0.55; 0.37-0.83 95% CI; p = 0.101). Conclusion: Among the survivors of COVID-19 in an acute geriatric hospital, a NRS ≥5 at admission was associated with a longer LOS, but not with mortality

Impact of imiglucerase supply constraint on the therapeutic management and course of disease in French patients with Gaucher disease type 1

In 2009, a worldwide supply constraint of imiglucerase led to treatment modifications or interruptions for patients with Gaucher disease (GD) type 1. In France, joint treatment recommendations were issued to protect the most vulnerable patients. This observational study evaluated the impact of imiglucerase treatment modifications on the clinical and biological course of GD