Long-Term Evaluation of Biomarkers in the Czech Cohort of Gaucher Patients.

A personalized treatment decision for Gaucher disease (GD) patients should be based on relevant markers that are specific to GD, play a direct role in GD pathophysiology, exhibit low genetic variation, reflect the therapy, and can be used for all patients. Thirty-four GD patients treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) were analyzed for platelet count, chitotriosidase, and tartrate-resistant acid phosphatase activity in plasma samples, and quantitative measurement of Lyso-Gb1 was performed in dried blood spots. In our ERT and SRT study cohorts, plasma lyso-GL1 correlated significantly with chito-triosidase (ERT: r = 0.

A cross-sectional, prospective ocular motor study in 72 patients with Niemann-Pick disease type C.

Objective: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC).

Methods: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers.

Sebelipase alfa for lysosomal acid lipase deficiency: 5-year treatment experience from a phase 2 open-label extension study.

Background And Aims: Lysosomal acid lipase deficiency is characterized by hepatomegaly and dyslipidaemia, which can lead to cirrhosis and premature atherosclerosis. Sebelipase alfa is an approved recombinant human lysosomal acid lipase. In an open-label extension study of adults with lysosomal acid lipase deficiency (LAL-CL04), sebelipase alfa treatment for 1 year reduced serum transaminase levels and liver fat content and improved serum lipid levels.

Otorhinolaryngological manifestations in 61 patients with mucopolysaccharidosis.

Objectives: The mucopolysaccharidoses (MPS) are inherited lysosomal storage disorders with multisystemic and highly variable clinical manifestation. ENT symptoms are common and early signs of MPS. The most common ENT diagnoses are chronic/recurrent rhinosinusitis, acute otitis media, otitis media with effusion, hearing loss and airway obstruction.

Disease characteristics, prognosis and miglustat treatment effects on disease progression in patients with Niemann-Pick disease Type C: an international, multicenter, retrospective chart review.

Background: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales.

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings.

Objectives: To evaluate the function of the oculomotor and vestibular systems and to correlate these findings with the clinical status of patients with Gaucher disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was to find oculomotor biomarkers for future clinical trials.

Methods: Twenty-six patients with GD3 were assessed for eligibility and 21 were able to perform at least one task.

Acetyl-dl-leucine in Niemann-Pick type C: A case series.

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.

Clinical Features of Lysosomal Acid Lipase Deficiency.

Objective: The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults.

Methods: Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset.

Results: A total of 49 patients were enrolled; 48 had confirmed LAL D.

Cataplexy and sleep disorders in Niemann-Pick type C disease.

Niemann-Pick disease type C (NP-C) is a rare and progressive autosomal recessive disease leading to disabling neurological manifestation and premature death. The disease is prone to underdiagnosis because of its highly heterogeneous presentation. NP-C is characterized by visceral, neurological, and psychiatric manifestation, and its clinical picture varies according to age at onset.

Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency.

Background & Aims: Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase.

Methods: Sebelipase alfa (1mg/kg or 3mg/kg) was infused every-other-week to eligible subjects.

Mucopolysaccharidosis type VI in Russia, Kazakhstan, and Central and Eastern Europe.

Background: The aim of this study was to describe the natural clinical course, incidence and prevalence of mucopolysaccharidosis type VI (MPS VI) in Russia, Kazakhstan, and Central and Eastern Europe.

Methods: Patients (n = 49) were identified by retrieving the data from eight international centers for MPS VI.

Results: A large number of patients presented with an attenuated phenotype (33%).

Attenuated osteoarticular phenotype of type VI mucopolysaccharidosis: a report of four patients and a review of the literature.

Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI, OMIM 253200) is caused by mutations in the gene coding for N-acetylgalactosamine-4-sulfatase (4-sulfatase, arylsulfatase B, ARSB, EC 3.1.6.

The use of elevated doses of genistein-rich soy extract in the gene expression-targeted isoflavone therapy for Sanfilippo disease patients.

Mucopolysaccharidoses (MPS) are severe, inherited metabolic disorders caused by storage of glycosaminoglycans (GAGs). Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is described as severe neurological type of MPS, characterized by rapid deterioration of brain functions. No therapy for Sanfilippo disease is approved to date, however, a specific substrate reduction therapy (SRT), called gene expression-targeted isoflavone therapy (GET IT), has been used as an experimental therapy.

Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease.

Unlabelled: Cholesteryl ester storage disease (CESD), an inherited deficiency of lysosomal acid lipase (LAL), is an underappreciated cause of progressive liver disease with no approved therapy. Presenting features include dyslipidemia, elevated transaminases, and hepatomegaly. To assess the clinical effects and safety of the recombinant human LAL, sebelipase alfa, nine patients received four once-weekly infusions (0.

The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause).

Background: The principal manifestations of type 1 Gaucher disease (GD) (increased risk of bleeding, anaemia, splenomegaly, hepatomegaly and bone disease) are likely to affect females during reproductive events such as menarche and menstruation; fertility, pregnancy, parity, delivery and lactation; and menopause. In order to determine the optimal management of female Gaucher patients based on available data, we examine reproductive events and GD in untreated and alglucerase and/or imiglucerase-treated females.

Methods: A panel of international clinicians experienced in the management of GD reviewed and presented evidence from peer-reviewed literature, a pharmacovigilance database on imiglucerase, and their own clinical experience to support discussions and recommendations.

1H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency.

Objective: Total creatine (tCr) constitutes one of the most prominent signals in human brain MR spectra. A significant decrease in the tCr signal indicates a severe disorder of creatine metabolism. We describe the potential of 1H MR spectroscopy in differential diagnosis of creatine transporter (SLC6A8) deficiency syndrome.