BackgroundA preliminary exploratory study shows solid agreement between the results of case reports and clinical study meta-analyses in mucopolysaccharidosis Type I (MPS-I) adult patients. The aim of the present study is to confirm previous results in another patient population, suffering from mucopolysaccharidosis Type II (MPS-II).MethodsA systematic review and meta-analysis of case reports published by April 2018 was conducted for MPS-II patients treated with enzyme replacement therapy (ERT). The study is reported in accordance with PRISMA and MOOSE guidelines (PROSPERO database code CRD42018093408). The assessed population and outcomes were the same as previously analyzed in a meta-analysis of MPS-II clinical studies. The primary endpoint was the percent of clinical cases showing improvement in efficacy outcome, or no harm in safety outcome after ERT initiation. A restrictive procedure to aggregate case reports, by selecting standardized and well-defined outcomes, was proposed. Different sensitivity analyses were able to evaluate the robustness of results.ResultsEvery outcome classified as “acceptable evidence group” in our case report meta-analysis had been graded as “moderate strength of evidence” in the aforementioned meta-analysis of clinical studies. Sensitivity, specificity, and positive-negative predictive values for results of both meta-analyses reached 100%, and were deemed equivalent.ConclusionsAggregating case reports quantitatively, rather than analyzing them qualitatively, may improve conclusions in rare diseases and personalized medicine. Additionally, we propose some methods to evaluate publication bias and heterogeneity of the included studies in a meta-analysis of case reports.

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Background: Niemann-Pick disease (NPD) is a rare autosomal recessive hereditary disease characterized by deficient activity of acid sphingomyelinase. Case presentation: We present a case of NPD type B with a unique compound heterozygosity for SMPD1 (NM_ 000543.4:c.[84delC];[96G > A]) in which both mutations that induce an early stop codon are located before the second in-frame initiation codon. The clinical presentation of the patient is compatible with NPD type B. She was initially diagnosed of Gaucher Disease, but her altered lipid profile led to a clinical suspicion of NPD. Combined high doses of atorvastatin and ezetimibe were given to treat the severe hypercholesterolemia. Conclusions: The pharmacological management of the lipid profile in these patients is important. A unique compound mutation in SMPD1 gene is described.