Left ventricular hypertrophy: do not forget Fabry disease. Diagnostic work-up and differential diagnosis.

Background: Left ventricular (LV) hypertrophy is a common clinical finding. Differential diagnosis includes Fabry disease, a rare and progressive, but treatable storage disease caused by deficiency of α-galactosidase A. However, diagnosis of Fabry is often hampered by its clinical heterogeneity, LV hypertrophy phenocopies and unawareness of the clinician.

A new multiplex analysis of glucosylsphingosine and globotriaosylsphingosine in dried blood spots by tandem mass spectrometry.

Background: Gaucher's and Fabry's disease are two of the most common treatable lysosomal storage diseases, and have a wide spectrum of clinical symptoms. Early detection is important, because timely initiation of treatments can improve the disease status and prevent complications. However disease manifestations develop in childhood, diagnosis is delayed until adulthood partly due to the limitations of the currently used diagnostic pathway.

Metachromatic leukodystrophy: To screen or not to screen?

Metachromatic leukodystrophy (MLD) is a neurodegenerative lysosomal storage disorder caused by biallelic pathogenic variants in the gene encoding arylsulfatase A. Disease onset is variable (with late infantile, early and late juvenile, and adult forms) and treatment options depend on age and disease symptoms at onset. In the past, allo-hematopoietic stem cell transplantation (allo-HSCT) has been the best treatment option, following strict selection criteria.

Severe dilated cardiomyopathy as an unusual clinical presentation in an infant with sialidosis type II.

We report a unique case of an infant with a severe dilated cardiomyopathy as the clinical presentation of sialidosis type II (OMIM 256550), a rare autosomal recessive inherited lysosomal storage disease that is characterized by partial or complete deficiency of α-neuraminidase, following mutations in the gene neuraminidase 1 (), located on the short arm of chromosome 6 (6p21.3). Accumulation of metabolic intermediates leads to severe morbidity, especially myoclonus, gait disturbances, cherry-red macules with secondary loss of visual acuity, impaired color vision and night blindness, and sometimes additional neurological findings such as seizures.

Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway.

Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients.

Vertebral Tongue-Like Deformity in Mucopolysaccharidosis VI.

Defective development of the anterior portion of the vertebral body at the thoracolumbar junction may be an important imaging clue in the diagnosis of mucopolysaccharidosis.

Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at < 4 years of age with phenylketonuria: results of the 3-year extension of the SPARK open-label, multicentre, randomised phase IIIb trial.

Background: During the initial 26-week SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) study, addition of sapropterin dihydrochloride (Kuvan®; a synthetic formulation of the natural cofactor for phenylalanine hydroxylase, tetrahydrobiopterin; BH), to a phenylalanine (Phe)-restricted diet, led to a significant improvement in Phe tolerance versus a Phe-restricted diet alone in patients aged 0-4 years with BH-responsive phenylketonuria (PKU) or mild hyperphenylalaninaemia (HPA). Based on these results, the approved indication for sapropterin in Europe was expanded to include patients < 4 years of age. Herein, we present results of the SPARK extension study (NCT01376908), evaluating the long-term safety, dietary Phe tolerance, blood Phe concentrations and neurodevelopmental outcomes in patients < 4 years of age at randomisation, over an additional 36 months of treatment with sapropterin.

Placental Findings in Lysosomal Storage Disease Diagnosis: A Case Report of Galactosialidosis.

. Lysosomal storage disorders (LSDs) are rare diseases with more than 50 different entities described today. The spectrum of phenotypes varies from severe to lethal and early-onset disease to mild and late onset.

Dietary practices in methylmalonic acidaemia: a European survey.

Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providing sufficient energy to avoid catabolism and to limit production of methylmalonic acid. The goal is to achieve normal growth, good nutritional status and the maintenance of metabolic stability. Aim To describe the dietary management of patients with MMA across Europe.

Emotional and behavioral problems, quality of life and metabolic control in NTBC-treated Tyrosinemia type 1 patients.

Background: Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and dietary phenylalanine and tyrosine restriction improves physical health and life expectancy in Tyrosinemia type 1 (TT1). However, neurocognitive outcome is suboptimal. This study aimed to investigate behavior problems and health-related quality of life (HR-QoL) in NTBC-dietary-treated TT1 and to relate this to phenylalanine and tyrosine concentrations.

The natural history of classic galactosemia: lessons from the GalNet registry.

Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet.

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients.

Background: Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.

Objective: This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy.

Galactosidase Alpha p.A143T Variant Fabry Disease May Result in a Phenotype With Multifocal Microvascular Cerebral Involvement at a Young Age.

Introduction: A 16-year-old male presented with episodic headaches and a brain magnetic resonance imaging (MRI) that showed multifocal punctate to patchy white matter lesions. The diagnosis of Fabry disease (FD) was suggested upon the finding of significantly reduced plasma alpha-galactosidase A activity (0.62 µmol/L or 13% of normal; normal range ≥ 1.

Raising Awareness of False Positive Newborn Screening Results Arising from Pivalate-Containing Creams and Antibiotics in Europe When Screening for Isovaleric Acidaemia.

While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded.

Dietary practices in propionic acidemia: A European survey.

Background: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance.

Aim: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines.

Methods: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014.

Dietary practices in isovaleric acidemia: A European survey.

Background: In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management.

Aim: To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014).

Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial.

Background: Sapropterin dihydrochloride, a synthetic formulation of BH, the cofactor for phenylalanine hydroxylase (PAH, EC 1.14.16.

Bone Health in Classic Galactosemia: Systematic Review and Meta-Analysis.

Introduction: Previous studies have reported an association between classic galactosemia (CG) and decreased bone mass. The primary objective of this systematic review with meta-analysis was to determine the extent of bone mineral density (BMD) Z-score reduction. Low BMD was defined as a Z-score ≤-2 standard deviations (SD).

International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up.

Classical galactosemia (CG) is an inborn error of galactose metabolism. Evidence-based guidelines for the treatment and follow-up of CG are currently lacking, and treatment and follow-up have been demonstrated to vary worldwide. To provide patients around the world the same state-of-the-art in care, members of The Galactosemia Network (GalNet) developed an evidence-based and internationally applicable guideline for the diagnosis, treatment, and follow-up of CG.

Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study.

Background: Fabry disease is an X-linked lysosomal storage disorder caused by mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant () forms of α-Gal to facilitate normal lysosomal trafficking.

Methods: The main objective of the 18-month, randomised, active-controlled ATTRACT study was to assess the effects of migalastat on renal function in patients with Fabry disease previously treated with ERT.