219 Incidence Testing of Hunter Syndrome in A Population at Risk - First Results of A Binational Screening Programme

Background Hunter syndrome (Mucopolysaccharidosis type II; X-linked inheritance; prevalence rate in Europe approximately 1:77000 male newborns) is a rare, progressive, multisystemic disease, caused by deficiency of the lysosomal enzyme Iduronate-2-sulfatase. Due to the very heterogeneous phenotype Hunter syndrome is often not diagnosed before pre-school age. This is unfortunate, because patients would significantly benefit from the earliest possible start of treatment containing enzyme replacement therapy. Early screening methods are possible, but due to the rarity of this disease they are too expensive to be performed in all newborns. An at-risk patient population screening provides opport…

Retrospective Analysis of Whole-Body Magnetic Resonance Imaging of Bone Manifestations in Long-Term Treated Patients with Gaucher Disease Type 1

We retrospectively assessed bone and visceral manifestations in patients with Gaucher disease type 1 (GD1) with whole-body magnetic resonance imaging (WB-MRI) to determine the effects of different timing in initiating long-term enzyme replacement therapy.In 17 patients with GD1, we performed 2 WB-MRI examinations at a median interval of 13 months. Patients had received enzyme replacement therapy with alglucerase/imiglucerase for a median of 13 years prior to the first examination. MRI results were retrospectively stratified based on treatment initiation into 2 groups: "early" (age ≤12 years, median 5 years) and "late" (during adulthood, median 32 years). We evaluated occurrence of irreversi…

Determination of globotriaosylceramide in plasma and urine by mass spectrometry

Abstract Background: Fabry disease is an X-chromosomally inherited lysosomal storage disorder leading to accumulation of glycosphingolipids, mainly globotriaosylceramide (ceramide-trihexoside, Gb3). Concentrations of Gb3 in plasma and urine have been used to diagnose Fabry disease and to monitor enzyme replacement therapy with recombinant α-galactosidase. Methods: Gb3 was purified from plasma or urine by combined liquid extraction/protein precipitation and solid-phase extraction, and was detected by flow-injection analysis electrospray mass spectrometry (MS) using multi-reaction-monitoring. Calibration was performed via standard addition using C17-Gb3 as internal standard. The most abundant…

The heart and cardiovascular system in patients with Morquio syndrome type A

Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease Patients with Use of Whole-Body MRI--A Retrospective Data Analysis.

Purpose: To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). Materials and Methods: This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15 – 29 years, mean age 22 years and Group B: 11 females, 8 males, 29 – 77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The…

Subclinical optic neuropathy in Fabry disease.

Fabry disease is a rare X-linked lysosomal storage disorder, caused by the deficiency of alpha-galactosidase A. Ophthalmic features comprise a cornea verticillata, conjunctival aneurysms, tortuous conjunctival and/or retinal vessels, and anterior and posterior subcapsular cataracts. The issue of a possible subclinical optic neuropathy in Fabry disease has been raised recently. In this pilot study, we looked for signs of optic neuropathy in our cohort of Fabry patients.Thirty-one Fabry patients (15 male, 16 female, mean age 34 years) underwent an ophthalmological investigation consisting of assessment of best corrected visual acuity, slit lamp investigation, testing of pupillary reaction, fu…

Acetyl-dl-leucine in Niemann-Pick type C

Objective: To assess the effects of the modified amino acid acetyl-dl-leucine (AL) on cerebellar ataxia, eye movements, and quality of life of patients with Niemann-Pick type C (NP-C) disease. Methods: Twelve patients with NP-C disease were treated with AL 3 g/d for 1 week and then with 5 g/d for 3 weeks with a subsequent washout period of 1 month. The Scale for the Assessment and Rating of Ataxia (SARA), the Spinocerebellar Ataxia Functional Index (SCAFI), the modified Disability Rating Scale (mDRS), EuroQol 5Q-5D-5L, and the visual analog scale (VAS) were administered. Measurements took place at baseline, after 1 month of therapy, and after 1 month of washout. Results: The SARA score chan…