IntroductionFabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD.MethodsA Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement.ResultsFor classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m2) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped.ConclusionThe recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0253-6) contains supplementary material, which is available to authorized users.

Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symptoms, and disease progression are heterogeneous, and patients may present with many different manifestations to a wide range of specialists. Expertise in diagnosing and managing MPS II varies widely between countries, and substantial delays between disease onset and diagnosis can occur. In recent years, disease-specific treatments such as enzyme replacement therapy and stem cell transplantation have helped to address the underlying enzyme deficiency in patients with MPS II. However, the multisystem nature of this disorder and the irreversibility of some manifestations mean that most patients require substantial medical support from many different specialists, even if they are receiving treatment. This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies.Take-home messageExpertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan-European recommendations for the diagnosis and management of this life-limiting disease.

Recurrence of CD is unaffected by the width of the margin of resection from macroscopically involved bowel. Recurrence rates also do not increase when microscopic CD is present at the resection margins. Therefore, extensive resection margins are unnecessary.

BackgroundMorquio A syndrome (or mucopolysaccharidosis IVa) is an ultra-rare multi-organ disease, resulting in significantly impaired functional capacity, mobility and quality of life (QoL).MethodsThis patient-reported outcomes survey evaluated the global burden of Morquio A among adults (≥18 years, N = 27) and children (7-17 years, N = 36), including the impact on mobility, QoL, pain and fatigue. QoL was assessed using the general Health-Related Quality of Life (HRQoL) questionnaire (the EuroQol [EQ]-5D-5L). Pain and pain interference with daily activities were assessed using the Brief Pain Inventory Short Form (BPI-SF) in adults and the Adolescent Pediatric Pain Tool (APPT) in children. Fatigue was assessed by questioning the patients on the number of evenings in a week they felt extremely tired.ResultsThe clinical data showed a wide heterogeneity in clinical manifestations between patients, with the majority of patients showing differing levels of endurance, short stature, bone and joint abnormalities, abnormal gait and eye problems. Mobility was considerably impaired: 44.4% of children and 85.2% of adult patients were using a wheelchair. High wheelchair reliance significantly reduced QoL. This was mainly driven by reduced scores in the Mobility, Self-care, and Usual Activity domains. The HRQoL utility values were 0.846, 0.582 and 0.057 respectively in adults not using a wheelchair, using a wheelchair only when needed and always using a wheelchair; values were 0.534, 0.664 and –0.180 respectively in children. Employed adult patients had a better HRQoL than unemployed patients (HRQoL utility value 0.640 vs. 0.275, respectively).64% of children and 74% of adult patients had joint pain; fatigue was reported by 69% of children and 63% of adults. Overall, increased mobility was associated with more severe and widespread pain and more fatigue.ConclusionsThe HRQoL of Morquio A patients is mainly driven by the ability to remain independently mobile without becoming wheelchair dependent. Their QoL reduces dramatically if they always have to use their wheelchair. Even a slightly better mobility (wheelchair use only when needed) greatly improves QoL. Maintenance of functional capacity and mobility paired with better pain management are likely to improve QoL.

Background: Morquio syndrome A (mucopolysaccharidosis type IVA) is an autosomal recessive, lifelimiting lysosomal storage disease characterized by deficient activity of the enzyme galactosamine-6-sulfatase. The disease affects multiple body systems, and patients require multidisciplinary care from an early age.Methods: To better understand the natural progression of the disease, life expectancy and common causes of death, death certificates were evaluated for 27 patients (15 male, 12 female) with Morquio syndrome A in the UK, covering the years 1975-2010.Results: Mean age at death (AEstandard deviation) was 25.30 AE 17.43 years, with female patients living longer than male patients (26.55 AE 12.28 years versus 22.95 AE 17.63 years, respectively). Respiratory failure was the primary cause of death in nearly two-thirds of patients (63%). Other causes of death were cardiac failure (11%), post-traumatic organ failure (11%), complications of surgery (11%) and myocardial infarction (4%). Life expectancy increased gradually over time (R 2 ¼ 0.0963), and mean age at death due to respiratory failure improved from 17.42 AE 9.54 years in the 1980s to 30.74 AE 10.84 years in the 2000s. Conclusions:The current data suggest that survival of patients with Morquio syndrome A in the UK has improved in recent decades. It is possible that improvements in multidisciplinary care and referral of patients to specialist centres underlie this trend. It is hoped that novel diseasespecific treatments such as enzyme replacement therapy and haematopoietic stem cell therapy will help to extend the lifespan of patients with Morquio syndrome further still.