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Background Mucopolysaccharidoses (MPS) are a group of rare inherited disorders characterized by abnormal accumulation of glycosaminoglycans (GAGs) within the myocytes and coronary arteries. Little is known about hyperlipidaemia as a potential cardiovascular risk factor in these patients. Baseline cholesterol data in adults are scarce. Therefore, the aim of this study was to analyse factors affecting lipid profile in different types of MPSs to determine if abnormalities in lipid profile contribute to the overall risk of cardiovascular disease. Methods Adult patients (above the age of 16) with MPS type I, II, III, IV and VI attending clinics in two Inherited Metabolic Disorders centres were included. Their lipid profile, lipoprotein (a), HbA1c, Glucose Tolerance Test (GTT), BMI and treatment type were extracted. Analysis included descriptive statistics and Student t-test. Results Eighty two patients with five MPS types (I, II, III, IV and VI) were included in the study; 29 were females (35%) and 53 were males (65%). BMI above 25 kg/m2 in all MPS types indicated that some patients were overweight for their height. Only one patient post-HSCT had diabetes. In 3 cases insulin was analysed during GTT and showed no insulin resistance despite raised BMI. Mean total cholesterol and LDL-cholesterol were below 5 mmol/L and 3 mmol/L, respectively, in five individual MPS types. Lipoprotein (a) was available for 6 MPS IV patients and was not significantly raised. Conclusions MPS disorders are not associated with significant hypercholesterolaemia or diabetes mellitus despite increased BMI. Total cholesterol and LDL-cholesterol were within the targets for primary prevention for non-MPS population. Lipoprotein (a) is not a useful marker of cardiovascular disease in a small group of adult MPS IV patients irrespectively of treatment option. Whether long-term cardiovascular risk is dependent on lipid profile, diabetes, obesity or GAGs deposition within the organ system remains unanswered.

Background Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III) is an inherited monogenic lysosomal storage disorder divided into subtypes A, B, C and D. Each subtype is characterized by deficiency of a different enzyme participating in metabolism of heparan sulphate. The resultant accumulation of this substrate in bodily tissues causes various malfunctions of organs, ultimately leading to premature death. Eighty-four, 24 and 5 death certificates of patients with Sanfilippo syndrome types A, B and C, respectively, were obtained from the Society of Mucopolysaccharide Diseases (UK) to better understand the natural course of these conditions, covering the years 1977–2007. Results In Sanfilippo syndrome type A mean age at death (± standard deviation) was 15.22 ± 4.22 years, 18.91 ± 7.33 years for patients with Sanfilippo syndrome type B and 23.43 ± 9.47 years in Sanfilippo syndrome type C. Patients with Sanfilippo syndrome type A showed significant increase in longevity over the period of observation (p = 0.012). Survival rates of patients with Sanfilippo syndrome type B did not show a statistically significant improvement (p = 0.134). In Sanfilippo syndrome types A and B, pneumonia was identified as the leading cause of death. Conclusions The analysis of 113 death certificates of patients with Sanfilippo syndrome in the UK has demonstrated that the longevity has improved significantly in patients with Sanfilippo syndrome type A over a last few decades. The numbers of patients with Sanfilippo syndrome types B and C were too small to identify any significant trend changes for these groups. Respiratory tract infections, notably pneumonia, remain the leading cause of mortality in Sanfilippo syndrome types A and B. The extended lifespans of patients with Sanfilippo syndrome type A were achieved despite the lack of therapies to target the primary insult or pathophysiology of the disease. However, the mean age at death of these patients remains low when compared with the general population. Therefore, there is an urgent need for effective disease-specific therapies to be developed so that the quality of life and survival of patients with Sanfilippo syndrome can be improved.

Introduction: Phenyloketonuria is a rare metabolic disorder caused by a deficiency of the phenylalanine (Phe) hydroxylase enzyme. A reduced intake of natural proteins helps optimise plasma Phe concentration. A relationship between high plasma Phe level and the inhibition of cholesterol synthesis was previously observed but the mechanisms are unclear. Low LDL-cholesterol concentrations were observed in children and adolescent PKU patients, but not in adults. This is the first paper to present lipid profile in adult patients with this condition. Methods: Lipid profile was analysed in adult patients with PKU. We examined associations between Phe and four outcomes: total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. Confounding factors (predictors) were taken into account: body mass index (BMI), age and gender. The statistical analysis was performed using multiple linear regression. Results: Among 176 adult patients 91 were females (52%). The mean age was 32 ± 10.7 years. 82 patients (46%) were on strict PKU diet. Mean Phe was 1017 ± 440 μmol/L. Mean total cholesterol was 4.33 ± 0.94 mmol/L, LDL-cholesterol 2.48 ± 0.8 mmol/L, HDL-cholesterol 1.2 ± 0.34 mmol/L, triglycerides 1.6 ± 0.9 mmol/L. There was no correlation between Phe concentration and lipid profile in our cohort of adult patients with PKU. No cardiovascular events were documented in our cohort. Conclusions: In conclusion, the outcomes of the study demonstrate that mean total cholesterol, LDL-cholesterol and triglycerides concentrations were substantially lower as compared to healthy population, which may confer their reduced cardiovascular risk. Lipid profile remained low irrespectively of Phe concentration.

Miglustat (Zavesca®) is approved for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease (GD1) for whom enzyme replacement therapy is unsuitable, and for the treatment of progressive neurological manifestations in adult and paediatric patients with Niemann-Pick disease type C (NP-C). Gastrointestinal disturbances such as diarrhoea, flatulence and abdominal pain/discomfort have consistently been reported as the most frequent adverse events associated with miglustat during clinical trials and in real-world clinical practice settings. These adverse events are generally mild or moderate in severity, occurring mostly during the initial weeks of therapy. The mechanism underlying these gastrointestinal disturbances is the inhibition by miglustat of intestinal disaccharidase enzymes (mainly sucrase and maltase), leading to sub-optimal hydrolysis of carbohydrates and subsequent osmotic diarrhoea and altered colonic fermentation. Transient decreases in body weight, which are often observed during initial miglustat therapy, are considered likely due to gastrointestinal carbohydrate malabsorption and associated negative caloric balance. While most cases of diarrhoea resolve spontaneously during continued miglustat therapy, diarrhoea also responds well to anti-propulsive medications such as loperamide. Dietary modifications such as reduced consumption of dietary sucrose, maltose and lactose have been shown to improve the gastrointestinal tolerability of miglustat and reduce the magnitude of any changes in body weight, particularly if initiated at or before the start of therapy. Miglustat dose escalation at treatment initiation may also reduce gastrointestinal disturbances. This article discusses these aspects in detail, and provides practical recommendations on how to optimize the gastrointestinal tolerability of miglustat.

Inherited metabolic disorders are becoming more important with the increasing availability of diagnostic methods and therapies for these conditions. The radiologist has become an important link in making the diagnosis or collaborating with the specialist centre to diagnose these disorders and monitor effects of therapy. The modes of presentation, disease-specific groups, classic radiological features and investigations are explored in this article to try and give the general radiologist some crucial background knowledge. The following presentations are covered: acute intoxication, hypoglycaemia, developmental delay and storage features. Specific groups of disorders covered are the abnormalities of intermediary metabolism, disorders of fatty acid oxidation and ketogenesis, mitochondrial disorders, lysosomal storage disorders, and, briefly, other groups such as peroxisomal disorders, disorders of glycosylation, and creatine synthesis disorders. New advances and the demands for monitoring are also briefly explored.

It seems like deja vu for those affected by rare diseases, and once again political change is to blame. Only two years ago the chief medical officer stated: “Services for those with rare diseases are fragmented and often poorly coordinated.”1 Commissioning of services for conditions individually affecting only 10% of the population presents challenges to value, fairness, and equity. Since 2005 the establishment of a UK National Commissioning Group for Rare Disorders (latterly National Specialist Commissioning Team) and Advisory Group for National Specialised Services …

Background Morquio A (MPS IVA) is a rare disease characterised by a deficiency of N-acetylgalactosamine-6 sulfatase (GALNS) and presenting with short stature, abnormal gait, cervical spine instability and shortened lifespan. Purpose To prepare a systematic review of the prevalence of Morquio A in multiple countries and suggest recommendations for reporting rare diseases. Methods Medline, Medline In-Process, Medline Daily Update, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database and PROSPERO were searched from inception to October 2013 to identify relevant information on the epidemiology of Morquio A. Forty Patient Organisation Representatives (POR) and Key Opinion Leaders (KOL) across 24 countries were contacted for data. Observational studies were included and case reports were excluded. Searches were performed without date or language restriction. Two researchers independently screened and extracted data. Quality of study reporting was assessed using a checklist adapted from STROBE (STrengthening the Reporting of OBservational studies in Epidemiology). Point or birth prevalence was stratified according to diagnostic method and discussed narratively. Results In total 9,074 records were retrieved from searching and 25 studies were included for data extraction. Twenty out of 40 KOL and POR responded (50%) and 9 provided data (23%). Point prevalence of Morquio A was 1 per 926,000 in Australia, 1 per 1,872,000 in Malaysia and 1 per 599,000 in UK and Morquio (unclassified) was 1 per 323, 000 in Denmark. Birth prevalence of Morquio A (using recommended diagnostic methods) ranged from 1 per 71,000 in UAE to 1 per 500,000 in Japan. All results were compromised by poor study reporting and internal validity. Conclusions The review highlighted that there is a misunderstanding of the definitions for prevalence and incidence in the field; that studies were poorly reported (diagnostic methods and patient characteristics) and that no suitable quality assessment tool exists. Overestimation and underestimation of prevalence data can occur. Bespoke reporting guidelines and a quality assessment tool specifically for prevalence of rare diseases are recommended. Electronic supplementary material The online version of this article (doi:10.1186/s13023-014-0173-x) contains supplementary material, which is available to authorized users.