Monitoring and integrated care coordination of patients with alpha-mannosidosis: A global Delphi consensus study.

Introduction: Current literature lacks consensus on initial assessments and routine follow-up care of patients with alpha-mannosidosis (AM). A Delphi panel was conducted to generate and validate recommendations on best practices for initial assessment, routine follow-up care, and integrated care coordination of patients with AM.

Methods: A modified Delphi method involving 3 rounds of online surveys was used.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome.

Study Design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected.

Reply to Curtis, L. Comment on "Magner et al. Sulforaphane Treatment in Children with Autism: A Prospective Randomized Double-Blind Study. 2023, , 718".

We thank Dr. Curtis for his interest and feedback [..

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.

Adenotonsillar pathology in mucopolysaccharidoses - lysosomal storage predominates in paracortical CD63+ cells.

Despite the adenoids are regularly removed in patients with mucopolysaccharidoses (MPS), the underlying tissue and cellular pathologies remain understudied. We characterized an (immuno)histopathologic and ultrastructural phenotype dominated by lysosomal storage changes in a specific subset of adenotonsillar paracortical cells in 8 MPS patients (3 MPS I, 3 MPS II, and 2 MPS IIIA). These abnormal cells were effectively detected by an antibody targeting the lysosomal membrane tetraspanin CD63.

Sulforaphane Treatment in Children with Autism: A Prospective Randomized Double-Blind Study.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with repetitive behaviour which affects interaction and communication. Sulforaphane (SFN), an isothiocyanate abundant in the seeds and sprouts of cruciferous vegetables, has been shown to be effective in alleviating autistic behaviour. We performed a prospective double-blind placebo-controlled study to examine the possible effect of SFN in a paediatric cohort aged three to seven years based on measurements of the Autism Diagnostic Observation Schedule-2 (ADOS-2), the Social Responsiveness Scale-2 (SRS-2), and the Aberrant Behaviour Checklist (ABC).

Deleterious, protein-altering variants in the transcriptional coregulator ZMYM3 in 27 individuals with a neurodevelopmental delay phenotype.

Neurodevelopmental disorders (NDDs) result from highly penetrant variation in hundreds of different genes, some of which have not yet been identified. Using the MatchMaker Exchange, we assembled a cohort of 27 individuals with rare, protein-altering variation in the transcriptional coregulator ZMYM3, located on the X chromosome. Most (n = 24) individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) harbor de novo variants.

GABBR1 monoallelic de novo variants linked to neurodevelopmental delay and epilepsy.

GABA receptors are obligatory heterodimers responsible for prolonged neuronal inhibition in the central nervous system. The two receptor subunits are encoded by GABBR1 and GABBR2. Variants in GABBR2 have been associated with a Rett-like phenotype (MIM: 617903), epileptic encephalopathy (MIM: 617904), and milder forms of developmental delay with absence epilepsy.

Transient Hyperphosphatasemia in a Child with Autism Spectrum Disorder.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. Transient hyperphosphatasemia of infancy and early childhood (THI) is a benign laboratory disorder characterized by transiently extremely elevated activity of serum alkaline phosphatase (S-ALP).

Case Report: We present a 21-month-old girl with a right leg limp, most probably due to reactive arthritis after febrile viral infection, and deterioration of psychomotor development with concomitant transient elevation of S-ALP (61.

Hearing Loss in Patients With Morquio Syndrome: Protocol for a Scoping Review.

Background: Mild to moderate hearing loss is common in patients with mucopolysaccharidosis (MPS) IVA. The hearing loss can be conductive, sensorineural, or mixed. However, in these patients, the mixed form is frequent, attributed to the combination of conductive and neurosensory elements, with slowly progressive evolution.

Consensus statement on enzyme replacement therapy for mucopolysaccharidosis IVA in Central and South-Eastern European countries.

Background: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. A progressive systemic skeletal chondrodysplasia, leading to significant morbidity and reduced life expectancy is the main clinical feature of this multisystemic disease. Although enzyme replacement therapy with elosulfase alfa is established in Europe, the rarity of disease and other factors still set hurdles in having patients treated in some countries.

Pitfalls of X-chromosome inactivation testing in females with Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene encoding alpha-galactosidase A (AGAL). The impact of X-chromosome inactivation (XCI) on the phenotype of female FD patients remains unclear. In this study we aimed to determine pitfalls of XCI testing in a cohort of 35 female FD patients.

The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers.

Background: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients.

Pontocerebellar atrophy is the hallmark neuroradiological finding in late-onset Tay-Sachs disease.

Purpose: Late-onset Tay-Sachs disease (LOTS) is a form of GM2 gangliosidosis, an autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia, lower motor neuron disease, and psychiatric impairment due to mutations in the HEXA gene. The aim of our work was to identify the characteristic brain MRI findings in this presumably underdiagnosed disease.

Methods: Clinical data and MRI findings from 16 patients (10F/6 M) with LOTS from two centers were independently assessed by two readers and compared to 16 age- and sex-related controls.

Factors Influencing Sulforaphane Content in Broccoli Sprouts and Subsequent Sulforaphane Extraction.

Broccoli sprouts contain 10-100 times higher levels of sulforaphane than mature plants, something that has been well known since 1997. Sulforaphane has a whole range of unique biological properties, and it is especially an inducer of phase 2 detoxication enzymes. Therefore, its use has been intensively studied in the field of health and nutrition.

The fission yeast S-phase cyclin Cig2 can drive mitosis.

Commitment to mitosis is regulated by cyclin-dependent kinase (CDK) activity. In the fission yeast Schizosaccharomyces pombe, the major B-type cyclin, Cdc13, is necessary and sufficient to drive mitotic entry. Furthermore, Cdc13 is also sufficient to drive S phase, demonstrating that a single cyclin can regulate alternating rounds of replication and mitosis, and providing the foundation of the quantitative model of CDK function.

White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis.

Objective: Despite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations.

Methods: Twenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls.

Searching for COVID-19 Antibodies in Czech Children-A Needle in the Haystack.

During the COVID-19 pandemics of 2020, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both adults and children were shown to mount a specific antibody response to the virus. As infected children often exhibit mild symptoms or even remain asymptomatic, they are likely to be under tested for the direct presence of the virus. Mapping the SARS-CoV-2 antibodies frequency informs more accurately on the disease prevalence and helps guide the protective and therapeutic strategies.

Combined valve replacement and aortocoronary bypass in an adult mucopolysaccharidosis type VII patient.

Mucopolysaccharidosis type VII (MPS VII) is a rare autosomal recessive lysosomal storage disorder. MPS VII is caused by mutations in the GUSB gene that encodes β-glucuronidase. Adult MPS VII patients present with musculoskeletal abnormalities, coarse features, and corneal clouding.