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International audience; A good understanding of the natural history of rare genetic lipid disorders is a pre-requisite for successful patient management. Disease registries have been helpful in this regard. Lipoprotein Lipase Deficiency (LPLD) is a rare, autosomal-recessive lipid disorder characterized by severe hypertriglyceridemia and a very high risk for recurrent acute pancreatitis, however, only limited data are available on its natural course. Alipogene tiparvovec (Glybera (R)) is the first gene therapy to receive Marketing Authorization in the European Union; GENIALL (GENetherapy In the MAnagement of Lipoprotein Lipase Deficiency), a 15-year registry focusing on LPLD was launched in 2014 as part of its Risk Management Plan. The aim of this publication is to introduce the GENIALL Registry within a structured literature review of registries in rare genetic lipid disorders. A total of 11 relevant initiatives/registries were identified (homozygous Familial Hypercholesterolemia (hoFH) [n = 5]; LPLD [n = 1]; Lysosomal Acid Lipase Deficiency [LALD, n = 1], detection of mutations in genetic lipid disorders [n = 4]). Besides one product registry in hoFH and the LALD registry, all other initiatives are local or country-specific. GENIALL is the first global prospective registry in LPLD that will collect physician and patient generated data on the natural course of LPLD, as well as long-term outcomes of gene therapy. Conclusion: There is a limited number of international initiatives focusing on the natural course of specific rare genetic lipid disorders. The GENIALL LPLD Registry could be the first step towards a future broader global initiative that collects data related to familial chylomicronemia syndrome and their underlying genetic causes. (C) 2016 Published by Elsevier Ireland Ltd.

Objectives: LPLD is an ultra-orphan genetic lipid disorder (prevalence 1-2/million). It is associated with severe hypertriglyceridemia and an increased risk of acute pancreatitis. Other manifestations include eruptive xanthoma, fatigue, difficulty with concentrating and cardiopulmonary symptoms. Associated symptoms, complications and the fat-restricted diet affect Quality of Life (QOL). Currently no disease-specific measure exists to assess QOL and the burden of LPLD. As part of post approval commitments of alipogene tiparvovec, regulatory bodies requested the development of a reliable measure of QOL in LPLD. This study evaluates existing EORTC questionnaires QLQ-C30 and QLQ-PAN26, and a new questionnaire of disease burden devised by clinicians with experience in treating LPLD. Methods: To date, eight genetically confirmed LPLD-patients from four countries assessed the relevance and importance of each item of the three questionnaires. Patients’ ratings were discussed during an in-depth, face-to-face interview and the disease burden questionnaire was comprehensively discussed, analyzed and then modified where necessary. Results: Quantitative assessment showed that 25 (45%) of the QLQ-C30 and QLQ-PAN26 questions were relevant to the majority of patients. The most relevant items were pain (6), fatigue and sleeping problems (4), digestive and dietary factors (4), work, daily and social activity restrictions (4) and impact on emotional functioning (3). Qualitative and quantitative analysis of the new questionnaire highlighted the unpredictability of pancreatitis attacks and the impact of the strict low fat diet on social and emotional factors. Less common clinical manifestations of LPLD (xanthoma, dyspnea) were very important to those affected. The new questionnaire has been modified and items on alcohol use and painkillers added for ongoing evaluation. Conclusions: Five QOL domains relevant to LPLD have been identified using existing questionnaires. A new disease-specific questionnaire identifies significant impacts on patients’ lives. These instruments may help clinicians to effectively use pharmacological and genetic therapy to manage LPLD patients.