BackgroundSanfilippo syndrome (mucopolysaccharidosis [MPS] III subtypes A, B, C, and D) is a rare autosomal recessive inherited metabolic disorder that causes progressive neurocognitive degeneration. This systematic literature review was undertaken to compile and assess published epidemiological data, including various frequency measures and geographical variation on Sanfilippo syndrome.MethodsThe following databases were systematically searched for terms related to Sanfilippo syndrome epidemiology: Medline, Embase, Cochrane Database of Systematic Reviews, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature, and the Centre for Reviews and Dissemination. Qualitative synthesis of research findings was performed.ResultsOf 2794 publications found in the initial search, 116 were deemed eligible after title and abstract screening. Following full-text review, 46 papers were included in the qualitative synthesis. Results of this systematic literature review indicate that lifetime risk at birth ranges from 0.17–2.35 per 100,000 live births for all 4 subtypes of MPS III together, and from 0.00–1.62 per 100,000 live births for the most frequent subtype, MPS IIIA.ConclusionAll 4 subtypes of MPS III are exceptionally rare, but they each have devastating effects on children. Higher-quality epidemiological data are needed to appropriately target resources for disease research and management.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0796-4) contains supplementary material, which is available to authorized users.

Methylmalonic acidemia/aciduria (MMA) is a genetically heterogeneous group of inherited metabolic disorders biochemically characterized by the accumulation of methylmalonic acid. Isolated MMA is primarily caused by the deficiency of methylmalonyl-CoA mutase (MMA mut; EC 5.4.99.2). A systematic literature review and a meta-analysis were undertaken to assess and compile published epidemiological data on MMA with a focus on the MMA mut subtype (OMIM #251000). Of the 1114 identified records, 227 papers were assessed for eligibility in full text, 48 articles reported on disease epidemiology, and 39 articles were included into the quantitative synthesis. Implementation of newborn screening in various countries has allowed for the estimation of birth prevalence of MMA and its isolated form. Meta-analysis pooled point estimates of MMA (all types) detection rates were 0.79, 1.12, 1.22 and 6.04 per 100,000 newborns in Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. The detection rate of isolated MMA was < 1 per 100,000 newborns in all regions with the exception of MENA where it approached 6 per 100,000 newborns. Few studies published data on the epidemiology of MMA mut, therefore no meta-analysis could have been performed on this subtype. Most of the identified papers reported birth prevalence estimates below 1 per 100,000 newborns for MMA mut. The systematic literature review clearly demonstrates that MMA and its subtypes are ultra-rare disorders. Electronic supplementary material The online version of this article (10.1186/s13023-019-1063-z) contains supplementary material, which is available to authorized users.

Propionic acidemia (PA, OMIM #606054) is a serious, life-threatening, inherited, metabolic disorder caused by the deficiency of the mitochondrial enzyme propionyl-coenzyme A (CoA) carboxylase (EC 6.4.1.3). The primary objective of this study was to conduct a systematic literature review and meta-analysis on the epidemiology of PA. The literature search was performed covering Medline, Embase, Cochrane Database of Systematic Reviews, CRD Database, Academic Search Complete, CINAHL and PROSPERO databases. Websites of rare disease organizations were also searched for eligible studies. Of the 2338 identified records, 188 articles were assessed for eligibility in full text, 43 articles reported on disease epidemiology, and 31 studies were included into the quantitative synthesis. Due to the rarity of PA, broadly targeted population-based prevalence studies are not available. Nonetheless, implementation of newborn screening programs has allowed the estimation of the birth prevalence data of PA across multiple geographic regions. The pooled point estimates indicated detection rates of 0.29; 0.33; 0.33 and 4.24 in the Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. Our systematic literature review and meta-analysis confirm that PA is an ultra-rare disorder, with similar detection rates across all regions with the exception of the MENA region where the disease, similar to other inherited metabolic disorders, is more frequent. Electronic supplementary material The online version of this article (10.1186/s13023-018-0987-z) contains supplementary material, which is available to authorized users.

were assessed for quality. Data on the cumulative incidence of cGVHD and related disease severity, and their predictive factors were extracted. RESULTS: After full text screening 84 articles were included. The 1-, 2-, and 5year cumulative incidence of cGVHD ranged from 14% to 60%, from 6% to 90%, and from 44% to 70%, respectively. Based on reviewed articles, age, gender, donor type, type of conditioning regimen, type of cGVHD prophylaxis, stem cell source, prior aGVHD, underlying disorders and immune system related factors (e.g. number of CD34+ cells or late activated T-cells) were predictors significantly affecting cGVHD. The 1-, 2-year cumulative incidence of moderate to severe cGVHD ranged from 8.6% to 42.6% and from 3.2% to 56.5%, respectively, while the 1-, 2-year cumulative incidence of severe cGVHD ranged from 2.2% to 13% and from 2.4% to 31.2%, respectively. The distribution of moderate and severe cGVHD patients among diagnosed cGVHD patients ranged from 15% to 84% and from 4% to 66%, respectively. CONCLUSIONS: cGVHD is a highly prevalent disorder in HSCT recipients. The high number of influencing parameters may explain the wide variation of observed cGVHD cumulative incidence. Most studies focused on the factors affecting cGVHD incidence; however, more evidence is needed on the predictors of disease severity.

were used to estimate the age-adjusted national prevalence of diagnosed HCU and PKU patients. RESULTS: Among 97.3 million patients in the MSN, 6,613 (0.068 per 1,000) had a diagnosis of HCU between 1/1/2010 and 12/31/2016, compared to 5,120 (0.053 per 1,000) with a PKU diagnosis. Of the HCU cases, 0.51% were ages 0e11 years and 80% were 45 years or older at the time of the first recorded diagnosis during the study period. For PKU cases, 53% were ages 0e11 years and 13% were 45 years or older. The estimated age-adjusted prevalence of diagnosed HCU in the US for 2017 was~0.01% (31,162 cases) vs. 0.005% (16,615 cases) for PKU. CONCLUSIONS: As expected, the highest proportion of diagnosed PKU was observed in the youngest age group (ages 0e11 years), likely due to infants being diagnosed through mandatory newborn screening. Conversely, the proportion of diagnosed HCU cases in the younger age group was approximately ten times smaller, implying that HCU patients are not diagnosed primarily at birth or during early childhood. This suggests that current newborn screening tests fail to capture the vast majority of HCU cases, with patients diagnosed at later ages, even into adulthood, when they present with symptoms or comorbid conditions indicative of HCU.OBJECTIVES: Approximately 1 in 200,000e335,000 people worldwide have homocystinuria (HCU) but it may be underdiagnosed. We examined incidence and prevalence of homocysteine (tHcy) testing and the frequency of tHcy levels >30 mmoles/L. METHODS: In the MarketScan© Lab Database (MSN), we identified commercially insured patients with claims for a tHcy test (1/1/2006e3/31/2016). Frequency of elevated tHcy test result >30 mmoles/L and medications prescribed were examined. Frequencies of select comorbidities were assessed, using International Classification of Diseases (ICD-9 and ICD10) codes. Incidence of first-time tHcy testing and incidence and prevalence of tHcy >30 mmoles/L were tabulated. RESULTS: Of 8.2 million MSN patients in the Lab database, 1.9 million were enrolled throughout 4/1/15e3/31/16. Of those, 0.8% (15,012) had a tHcy test since 2006 (mean±SD, 10.8 ±15.1 mmoles/L). Of the 15,012 patients, 223 (1.5%) had tHcy >30 (96.0±174.1, median 39.9). Of the 223, 45% were diagnosed with hypertension, 44% hyperlipidemia, 17% hypothyroidism, 15% vitamin D deficiency and 12% renal disease, with only 10% (22) diagnosed with HCU or a sulfur amino acid metabolism disorder. After a tHcy >30 result, 11% were prescribed antihypertensives, 10% lipidlowering drugs, 9% anxiolytics or antidepressants, 7% thyroid hormone and 2% vitamin D. Annual incidence of a first tHcy test result was 0.8e2.3 (mean 1.5) tests/ 1000 person years in 2009e2015. The incidence of a first tHcy result >30 was 0.01e0.06 (mean 0.03)/1000. Estimated point prevalence of tHcy >30 in the U.S. on 4/ 1/2016 was~0.010%e 0.014% (33,562e43,706). CONCLUSIONS: This study is one of the first to estimate the prevalence of tHcy levels in the range of classical HCU in the U.S. Of patients having many symptoms associated wit...