Hurler syndrome (HS) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Hematopoietic stem cell transplantation (HSCT) results in long-term survival, although with significant residual disease burden. How this residual disease affects the health-related quality of life is unknown. Therefore, we conducted a multicenter cohort study on functional and

Background In patients with GTP-cyclohydrolase deficient dopa-responsive dystonia (DRD) the occurrence of associated non-motor symptoms (NMS) is to be expected. Earlier studies report conflicting results with regard to the nature and severity of NMS. The aim of our study was to investigate the prevalence of psychiatric disorders, sleep problems, fatigue and health-related quality of life (HR-QoL)

BACKGROUND: Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/or invasive diagnostic testing. A previous retrospective study in a research setting showed promising results with diagnoses in 57%, but patients were highly selected for known and likely Mendelian disorders. The aim of our prospect

In recent years the number of disorders known to affect amino acid synthesis has grown rapidly. Nor is it just the number of disorders that has increased: the associated clinical phenotypes have also expanded spectacularly, primarily due to the advances of next generation sequencing diagnostics. In contrast to the “classical” inborn errors of metabolism in catabolic pathways, in which elevated lev

Background: North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and

Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic me

Background: Genetic disorders causing dystonia show great heterogeneity. Recent studies have suggested that next-generation sequencing techniques such as gene panel analysis can be effective in diagnosing heterogeneous conditions. The objective of this study was to investigate whether dystonia patients with a suspected genetic cause could benefit from the use of gene panel analysis. Methods: In th

In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression network approach. The spinocerebellar ataxias are a group of neurodegenerative disorders characterized by coordination problems caused mainly by atrophy of the cerebellum. The dystonias are another group of neurological movement diso

We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleteriousness based on CADD scores for >3000 genes. In a benchmark on 18 clinical gene sets, we achieve a sen

Objectives: Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Methods: Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 chil

A broad range of rare inherited metabolic disorders can present with dystonia. For clinicians, it is important to recognize dystonic features, but it can be complicated by the mixed and complex clinical picture seen in many neurometabolic patients. Careful phenotyping is the first step towards the diagnosis of the underlying condition and subsequent targeted treatment, further supported by imaging

Background: Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and

BACKGROUND Three- pregnancies with male offspring in one family were complicated by severe polyhydramnios and prematurity. One fetus died; the other two had transient massive salt-wasting and polyuria reminiscent of antenatal Bartter's syndrome. METHODS To uncover the molecular cause of this possibly X-linked disease, we performed wholeexome sequencing of DNA from two members of the index family a

Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions. Emerging data describe high prevalences of non-motor symptoms, including psychiatric co-morbidity, as part of the phenotype of dystonia. Basal ganglia serotonin and serotonin-dopamine interactions gain attention, as imbalances are known to be involved in extrapyramidal movement and psychiat

Background Isolated (sub)acute chorea in young patients is a relatively rare movement disorder with a broad differential diagnosis, including drug-induced, post-infectious, auto-immunological and vascular aetiologies. Case presentation We describe an adolescent girl with Down's syndrome presenting with chorea due to oral contraceptive usage. After discontinuation of the oral contraceptive it took

Background: Many inborn errors of metabolism (IEMs) may present as sudden infant death (SID). Nowadays, increasing numbers of patients with IEMs are identified pre-symptomatically by population neonatal bloodspot screening (NBS) programmes. However, some patients escape early detection because their symptoms and signs start before NBS test results become available, they even die even before the sa

Aim: To investigate the interobserver agreement on phenotypic early-onset ataxia (EOA) assessment and to explore whether the Scale for Assessment and Rating of Ataxia (SARA) could provide a supportive marker. Method: Seven movement disorder specialists provided independent phenotypic assessments of potentially ataxic motor behaviour in 40 patients (mean age 15y [range 5-34]; data derived from Univ