It is estimated that the prevalence of persons with rare diseases in Norway is approximately 30 000, a number that has increased due to new technology that makes it possible to describe new diseases. In Norway, a disease is termed rare if the prevalence is less than 1 case in 10 000 people. Overall, more than 80% of rare
diseases are caused by genetic defects. Lymphoedema cholestasis syndrome 1 (LCS1), or Aagenaes syndrome, is one such rare disease, with nearly 100 diagnosed cases worldwide. Oystein Aagenaes, for whom the disease is named, was one of the first to describe this disease in 1968. Most patients originate from south-western Norway. Presently a total of 48 persons in Norway have been diagnosed with LCS1. The large number of cases recorded within our country is believed to be due to a founder effect.
The main challenge in these patients is neonatal cholestasis which causes malabsorption of fat and fat-soluble vitamins. If untreated, the condition leads to rickets, neuropathy and serious growth retardation or death due to haemorrhage. In some patients, cholestasis leads to end-stage liver disease. In adult patients, although periods of recurrent cholestasis might be distressing, primary lymphoedema is typically a greater concern. The overall aim of this work has been to obtain new evidence-based knowledge about the progression of liver disease in a group of adolescent and adult patients with LCS1, to evaluate the need for the treatment of liver disease outside cholestatic periods or the treatment of lymphoedema. These aims have been supported by the Centre for Rare Disorders (SSD), one of ten nationwide interdisciplinary competence centres working with rare diseases on the behalf of the Norwegian Ministry of Health and Care Services.
In conclusion, although the overall prognosis in LCS1 is highly variable, and is largely dependent on the progression of cholestasis, patients with LCS1 exhibit a relatively good prognosis compared with other types of hereditary neonatal cholestasis. More than 50% of patients can probably expect a normal life span. Data presented in this thesis show that adults who have survived the initial prolonged period of cholestasis and exhibit stable liver disease may have an even better prognosis. Approximately one-third of patients with LCS1 exhibit severe extremity lymphoedema and require close follow-up; however, lymphoedema is generally well managed with compression of lower limbs and CDT treatment. The diet of the LCS1 patient group is similar to that of healthy controls, with only few deviations from the Norwegian dietary recommendations. Overall, the care and follow-up of LCS1 patients in this group seems satisfactory, but patients could benefit from following Norwegian dietary guidelines, with specific emphasis on carbohydrate and fat quality, in addition to regular monitoring of the blood levels of vitamins D and E. The findings presented in this paper may provide potentially valuable information for adult LCS1 patients worldwide.
List of papers
(removed due to publisher restrictions)
Paper I: Monica Drivdal, Torleif Trydal, Tor-Arne Hagve, Ingunn Bergstad and Øystein Aagenæs. Prognosis, with evaluation of general biochemistry, of liver disease in lymphoedema cholestasis syndrome 1 (LCS1/ Aagenaes syndrome). Scandinavian Journal of Gastroenterology, 2006; 41: 469 -/475. DOI: 10.1080/00365520500335183
Paper II: Monica Drivdal, Elin Bjørge Løken, Tor-Arne Hagve, Ingunn Bergstad, Øystein Aagenæs. Do patients with lymphoedema cholestasis syndrome 1/ Aagenaes syndrome need dietary counselling outside cholestatic episodes? Clinical Nutrition 29 (2010) 525–530. DOI: 10.1016/j.clnu.2010.01.010
Paper III: Monica Drivdal, Carl-Erik Slagsvold, Øystein Aagenæs and Bengt Frode Kase. Hereditary lymphedema, characteristics and variations in 17 adult patients with Lymphedema Cholestasis Syndrome 1 (LCS1)/ Aagenaes syndrome. Lymphatic Research & Biology. Accepted 29th of June 2014. DOI: 10.1089/lrb.2014.0003
Paper IV: Monica Drivdal, Kirsten B Holven, Kjetil Retterstøl, Øystein Aagenæs and Bengt Frode Kase. A nine year follow-up of patients with lymphedema cholestasis syndrome 1 (LCS1/ Aagenaes syndrome). Manuscript