BACKGROUND: Heart transplantation is considered to be the gold standard treatment for selected patients with end-stage heart disease when medical therapy has been unable to halt progression of the underlying pathology. Evidence suggests that aerobic exercise training may be effective in reversing the pathophysiological consequences associated with cardiac denervation and prevent immunosuppression-induced adverse effects in heart transplant recipients. OBJECTIVES: to determine the effectiveness and safety of exercise-based rehabilitation on the mortality, hospital admissions, adverse events, exercise capacity, health-related quality of life, return to work and costs for people after heart transplantation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and Web of Science Core Collection (Thomson Reuters) to June 2016. We also searched two clinical trials registers and handsearched the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of parallel group, cross-over or cluster design, which compared exercise-based interventions with (i) no exercise control (ii) a different dose of exercise training (e.g. low- versus high-intensity exercise training); or (iii) an active intervention (i.e. education, psychological intervention). The study population comprised adults aged 18 years or over who had received a heart transplant. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on pre-specified inclusion criteria. Disagreements were resolved by consensus or by involving a third person. Two review authors extracted outcome data from the included trials and assessed their risk of bias. One review author extracted study characteristics from included studies and a second author checked them against the trial report for accuracy. MAIN RESULTS: We included 10 RCTs that involved a total of 300 participants whose mean age was 54.4 years. Women accounted for fewer than 25% of all study participants. Nine trials which randomised 284 participants to receive exercise-based rehabilitation (151 participants) or no exercise (133 participants) were included in the main analysis. One cross-over RCT compared high-intensity interval training with continued moderate-intensity training in 16 participants. We reported findings for all trials at their longest follow-up (median 12 weeks).Exercise-based cardiac rehabilitation increased exercise capacity (VO2peak) compared with no exercise control (MD 2.49 mL/kg/min, 95% CI 1.63 to 3.36; N = 284; studies = 9; moderate quality evidence). There was evidence from one trial that high-intensity interval exercise training was more effective in improving exercise capacity than continuous moderate-intensity exercise (MD 2.30 mL/kg/min, 95% CI 0.59 to 4.01; N = 16; 1 study). Four studies reported health-related quality of life (HRQoL) measured using SF-36, Profile of Quality of Life in the Chronically Ill (PLC) and the World Health Organization Quality of Life (WHOQoL) - BREF. Due to the variation in HRQoL outcomes and methods of reporting we were unable to meta-analyse results across studies, but there was no evidence of a difference between exercise-based cardiac rehabilitation and control in 18 of 21 HRQoL domains reported, or between high and moderate intensity exercise in any of the 10 HRQoL domains reported. One adverse event was reported by one study.Exercise-based cardiac rehabilitation improves exercise capacity, but exercise was found to have no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients whose health is stable.There was no evidence of statistical heterogeneity across trials for exercise capacity and no evidence of small study bias. The overall risk of bias in included studies was judged as low or unclear; more than 50% of included studies were assessed at unclear risk of bias with respect to allocation concealment, blinding of outcome assessors and declaration of conflicts of interest. Evidence quality was assessed as moderate according to GRADE criteria. AUTHORS' CONCLUSIONS: We found moderate quality evidence suggesting that exercise-based cardiac rehabilitation improves exercise capacity, and that exercise has no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients. Cardiac rehabilitation appears to be safe in this population, but long-term follow-up data are incomplete and further good quality and adequately-powered trials are needed to demonstrate the longer-term benefits of exercise on safety and impact on both clinical and patient-related outcomes, such as health-related quality of life, and healthcare costs.

BACKGROUND: Coronary heart disease (CHD) is the most common cause of death globally, although mortality rates are falling. Psychological symptoms are prevalent for people with CHD, and many psychological treatments are offered following cardiac events or procedures with the aim of improving health and outcomes. This is an update of a Cochrane systematic review previously published in 2011. OBJECTIVES: to assess the effectiveness of psychological interventions (alone or with cardiac rehabilitation) compared with usual care (including cardiac rehabilitation where available) for people with CHD on total mortality and cardiac mortality; cardiac morbidity; and participant-reported psychological outcomes of levels of depression, anxiety, and stress; and to explore potential study-level predictors of the effectiveness of psychological interventions in this population. SEARCH METHODS: We updated the previous Cochrane Review searches by searching the following databases on 27 April 2016: CENTRAL in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of psychological interventions compared to usual care, administered by trained staff, and delivered to adults with a specific diagnosis of CHD. We selected only studies estimating the independent effect of the psychological component, and with a minimum follow-up of six months. The study population comprised of adults after: a myocardial infarction (MI), a revascularisation procedure (coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and adults with angina or angiographically defined coronary artery disease (CAD). RCTs had to report at least one of the following outcomes: mortality (total- or cardiac-related); cardiac morbidity (MI, revascularisation procedures); or participant-reported levels of depression, anxiety, or stress. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all references for eligibility. A lead review author extracted study data, which a second review author checked. We contacted study authors to obtain missing information. MAIN RESULTS: This review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology.Moderate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low).There was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (β = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (β = -0.28, P = 0.03). AUTHORS' CONCLUSIONS: This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).

Background Although recommended in guidelines for the management of coronary heart disease (CHD), concerns have been raised about the applicability of evidence from existing meta-analyses of exercise-based cardiac rehabilitation (CR). Objectives the goal of this study is to update the Cochrane systematic review and meta-analysis of exercise-based CR for CHD. Methods the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and Science Citation Index Expanded were searched to July 2014. Retrieved papers, systematic reviews, and trial registries were hand-searched. We included randomized controlled trials with at least 6 months of follow-up, comparing CR to no-exercise controls following myocardial infarction or revascularization, or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data, and assessed risk of bias. Studies were pooled using random effects meta-analysis, and stratified analyses were undertaken to examine potential treatment effect modifiers. Results a total of 63 studies with 14,486 participants with median follow-up of 12 months were included. Overall, CR led to a reduction in cardiovascular mortality (relative risk: 0.74; 95% confidence interval: 0.64 to 0.86) and the risk of hospital admissions (relative risk: 0.82; 95% confidence interval: 0.70 to 0.96). There was no significant effect on total mortality, myocardial infarction, or revascularization. The majority of studies (14 of 20) showed higher levels of health-related quality of life in 1 or more domains following exercise-based CR compared with control subjects. Conclusions This study confirms that exercise-based CR reduces cardiovascular mortality and provides important data showing reductions in hospital admissions and improvements in quality of life. These benefits appear to be consistent across patients and intervention types and were independent of study quality, setting, and publication date.

BACKGROUND Although recommended in guidelines for the management of coronary heart disease (CHD),
concerns have been raised about the applicability of evidence from existing meta-analyses of exercise-based cardiac
rehabilitation (CR).
OBJECTIVES the goal of this study is to update the Cochrane systematic review and meta-analysis of exercise-based
CR for CHD.
METHODS the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and Science Citation Index
Expanded were searched to July 2014. Retrieved papers, systematic reviews, and trial registries were hand-searched.
We included randomized controlled trials with at least 6 months of follow-up, comparing CR to no-exercise controls
following myocardial infarction or revascularization, or with a diagnosis of angina pectoris or CHD defined by angiography.
Two authors screened titles for inclusion, extracted data, and assessed risk of bias. Studies were pooled using
random effects meta-analysis, and stratified analyses were undertaken to examine potential treatment effect modifiers.
RESULTS a total of 63 studies with 14,486 participants with median follow-up of 12 months were included. Overall, CR
led to a reduction in cardiovascular mortality (relative risk: 0.74; 95% confidence interval: 0.64 to 0.86) and the risk of
hospital admissions (relative risk: 0.82; 95% confidence interval: 0.70 to 0.96). There was no significant effect on total
mortality, myocardial infarction, or revascularization. The majority of studies (14 of 20) showed higher levels of healthrelated
quality of life in 1 or more domains following exercise-based CR compared with control subjects.
CONCLUSIONS This study confirms that exercise-based CR reduces cardiovascular mortality and provides important
data showing reductions in hospital admissions and improvements in quality of life. These benefits appear to be
consistent across patients and intervention types and were independent of study quality, setting, and publication date.

Background
Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an
increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac
rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review
previously published in 2011.
Objectives
To assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or
educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD.
To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD.
Search methods
We updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid),
CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014).
Selection criteria
We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months’ follow-up, compared with a
no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary
artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We
included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related
quality of life (HRQL), or costs. Data collection and analysis
Two review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria.
One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified
meta-analysis by the duration of follow up of trials, i.e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term:
> 3 years.
Main results
This review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants).
The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the
trials ranged from 47.5 to 71.0 years.Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor,
although there was evidence of an improvement in quality of reporting in more recent trials.
As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting
findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality
compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality
with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82,
95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29
trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04).
There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for
MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies
using univariate meta-regression. Results show that benefits in outcomes were independent of participants’ CHD case mix (proportion
of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication
date, setting (centre vs home-based), study location (continent), sample size or risk of bias.
Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20
trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with
exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a
potentially cost-effective use of resources in terms of gain in quality-adjusted life years.
The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence
varied widely by outcome and ranged from low to moderate.
Authors’ conclusions
This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control,
exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of
hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL
with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the
population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well
conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable
angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality
and hospital admissions, and assess costs and cost-effectiveness.

This is the protocol for a review and there is no abstract. The objectives are as follows: to determine the effectiveness and safety of exercise-based rehabilitation on the mortality, hospital admissions, morbidity, exercise capacity, health-related quality of life, and return to work of people after heart transplantation.

BACKGROUND: Overviews are a new approach to summarising evidence and synthesising results from related systematic reviews. OBJECTIVES: to conduct an overview of Cochrane systematic reviews to provide a contemporary review of the evidence for delivery of cardiac rehabilitation, to identify opportunities for merging or splitting existing Cochrane reviews, and to identify current evidence gaps to inform new cardiac rehabilitation systematic review titles. METHODS: We searched the Cochrane Database of Systematic Reviews (2014, Issue 10) to identify systematic reviews that addressed the objectives of this overview. We assessed the quality of included reviews using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) measurement tool and the quality of the evidence for reported outcomes using the GRADE framework. The focus of the data presentation was descriptive with detailed tabular presentations of review level and trial level characteristics and results. MAIN RESULTS: We found six Cochrane systematic reviews and judged them to be of high methodological quality. They included 148 randomised controlled trials (RCTs) in 98,093 participants. Compared with usual care alone, the addition of exercise-based cardiac rehabilitation in low-risk people after myocardial infarction or percutaneous coronary intervention or with heart failure appeared to have no impact on mortality, but did reduce hospital admissions and improved health-related quality of life. Psychological- and education-based interventions alone appeared to have little or no impact on mortality or morbidity but may have improved health-related quality of life. Home- and centre-based programmes were equally effective in improving quality of life outcomes at similar healthcare costs. Selected interventions can increase the uptake of cardiac rehabilitation programmes whilst there is currently only weak evidence to support interventions that improve adherence to cardiac rehabilitation programmes. The quality of the primary RCTs in the included systematic reviews was variable, and limitations in the methodological quality of the RCTs led to downgrading of the quality of the evidence, which varied widely by review and by outcome. AUTHORS' CONCLUSIONS: Exercise-based cardiac rehabilitation is an effective and safe therapy to be used in the management of clinically stable people following myocardial infarction or percutaneous coronary intervention or who have heart failure. Future RCTs of cardiac rehabilitation need to improve their reporting methods and reflect the real world practice better including the recruitment of higher risk people and consideration of contemporary models of cardiac rehabilitation delivery, and identify effective interventions for enhancing adherence to rehabilitation.

INTRODUCTION: Overviews are a new approach to summarising evidence and synthesising results from related systematic reviews. OBJECTIVES: to conduct an overview of Cochrane systematic reviews to provide a contemporary review of the evidence for cardiac rehabilitation (CR), identify opportunities for merging or splitting existing Cochrane reviews, and identify current evidence gaps to inform new review titles. METHODS: the Cochrane Database of Systematic Reviews was searched to identify reviews that address the objectives of this overview. Data presentation is descriptive with tabular presentations of review- and trial-level characteristics and results. RESULTS: the six included Cochrane systematic reviews were of high methodological quality and included 148 randomised controlled trials in 97,486 participants. Compared to usual care alone, exercise-based CR reduces hospital admissions and improves patient health related quality of life (HRQL) in low to moderate risk heart failure and coronary heart disease (CHD) patients. At 12 months or more follow-up, there was evidence of some reduction in mortality in patients with CHD. Psychological- and education-based interventions appear to have little impact on mortality or morbidity but may improve HRQL. Home- and centre-based programmes are equally effective in improving HRQL at similar costs. Selected interventions can increase the uptake of CR programmes but evidence to support interventions that improve adherence is weak. CONCLUSIONS: This overview confirms that exercise-based CR is effective and safe in the management of clinically stable heart failure and post-MI and PCI patients. We discuss the implications of this overview on the future direction of the Cochrane CR reviews portfolio.

OBJECTIVES: to determine the effectiveness of enzyme replacement therapy (ERT) for adults with late-onset Pompe disease. DESIGN: a longitudinal cohort study including prospective and retrospective clinical outcome data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data. PARTICIPANTS: Consenting adults (N = 62) with a diagnosis of late-onset Pompe disease who attended a specialist treatment centre in England. This cohort represented 83 % of all patients in the UK with a confirmed diagnosis of this rare condition. At study entry, all but three patients were receiving ERT (range of treatment duration, 0 to 3.1 years). OUTCOME MEASURES: Percent predicted forced vital capacity (%FVC); ventilation dependency; mobility; 6 min walk test (6MWT); muscle strength and body mass index (BMI). RESULTS: an association was found between time on ERT and significant increases in the distance walked in the 6MWT (p 

OBJECTIVES: to determine the effectiveness of enzyme replacement therapy (ERT) for adults and children with Fabry disease. DESIGN: Cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment and untreated patients contributed natural history data. PARTICIPANTS: Consenting adults (N = 289) and children (N = 22) with a confirmed diagnosis of Fabry disease attending a specialist Lysosomal Storage Disorder treatment centre in England. At recruitment 211 adults and seven children were on ERT (range of treatment duration, 0 to 9.7 and 0 to 4.2 years respectively). OUTCOME MEASURES: Clinical outcomes chosen to reflect disease progression included left ventricular mass index (LVMI); proteinuria; estimated glomerular filtration rate (eGFR); pain; hearing and transient ischaemic attacks (TIA)/stroke. RESULTS: We found evidence of a statistically significant association between time on ERT and a small linear decrease in LVMI (p = 0.01); a reduction in the risk of proteinuria after adjusting for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (p 

OBJECTIVES: to determine the effectiveness of enzyme replacement therapies (ERT) for adults with Gaucher disease (GD). DESIGN: a longitudinal, multi-centre cohort study, including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data. PARTICIPANTS: Consenting adults (N = 150, aged 16 to 83 years) with a diagnosis of GD who attended a specialist treatment centre in England. At recruitment, 131 patients were receiving ERT (mean treatment duration, 10.8 years; range 0-18 years). OUTCOME MEASURES: Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin; absence/presence of bone pain; spleen and liver volumes and AST levels. RESULTS: One hundred and fifty adults were recruited. Duration of ERT was associated with statistically significant improvements in platelet count (p 

OBJECTIVES: to determine the effectiveness of enzyme replacement therapies (ERT) for children with Gaucher disease (GD). DESIGN: a longitudinal cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Children on treatment contributed data before and during treatment. Children not on treatment contributed natural history data. PARTICIPANTS: Consenting children (N = 25, aged 1.1 to 15.6 years) with a diagnosis of GD (14 with GD1 and 11 with GD3) who attended a specialist treatment centre in England. At recruitment, 24 patients were receiving ERT (mean treatment duration, 5.57 years; range 0-13.7 years). OUTCOME MEASURES: Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin and absence/presence of bone pain. RESULTS: Duration of ERT was associated with statistically significant improvements in platelet count (p 

Lysosomal storage disorders (LSDs) comprise more than 50 extremely rare, inherited metabolic diseases resulting from a deficiency of specific lysosomal enzymes required for normal macromolecular metabolism. The National Collaborative Study for Lysosomal Storage Disorders (NCS-LSD), was a longitudinal cohort study which collected prospective and retrospective clinical data, and patient-reported data from adults and children with a confirmed diagnosis of Gaucher disease, Fabry disease, mucopolysaccharidosis type I (MPS I), mucopolysaccharidosis type II (MPS II), Pompe disease and Niemann Pick disease type C (NPC) in the UK. The study aimed to determine the natural history of these conditions and estimate the effectiveness and cost of therapies. Clinical outcomes were chosen to reflect disease progression. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment while untreated patients contributed natural history data. A total of 711 adults and children were recruited to this study from the seven LSD treatment centres in England. Data was collected from 2008 to 2011. This paper describes the methods used to collect and analyse clinical data for this study. The clinical findings are reported separately in a series of condition-specific articles in this issue.