key: cord-0738264-bcz2sohe
authors: Wilke, Matheus V.; de Souza, Carolina Fischinger Moura; Giugliani, Roberto; Schwartz, Ida V.
title: Informing patients with rare diseases about COVID-19: Creation of the “Beto and the Coronavirus” booklet
date: 2021-02-28
journal: Molecular Genetics and Metabolism
DOI: 10.1016/j.ymgme.2020.12.276
sha: dc6b3d46928bb12cf0aa5bd55af6b0c01608a0e2
doc_id: 738264
cord_uid: bcz2sohe

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dose-related reduction of α-galactosidase (to 39% of untreated αgalactosidase in 40 μM drug; b1% of control at 100 mM). These studies also showed reduction of heat-and pH-labile lysosomal enzyme hexosaminidase. However, more stable lysosomal hexosaminidase B, β-galactosidase, β -glucuronidase were only moderately reduced by chloroquine; cytosolic lactate dehydrogenase and malate dehydrogenase were unchanged. The specificity of chloroquine for a number of lysosomal enzymes was observed in a pattern comparable to rates of enzyme inactivation under conditions of pH neutralization. Of activities studied, α-galactosidase was most sensitive. These observations suggest that the chloroquine-induced phenocopy is the relative neutralization of lysosomes and accumulation of α-galactosidase substrates. It further warns against concomitant use of chloroquine-like medications in lysosomal diseases. Metachromatic leukodystrophy (MLD) is a rare, fatal autosomalrecessive genetic disorder caused by insufficient activity of the enzyme arylsulfatase A (ARSA) that results in intra-lysosomal accumulation of the ARSA substrate galactosylceramide I 3 -sulfate (sulfatide), inevitably leading to progressive demyelination and neurodegeneration in the CNS and PNS. There are three variants of MLD commonly described in the literature based on the age at which symptoms appear: late-infantile MLD, juvenile MLD, and adult MLD. All forms of MLD share the same underlying pathophysiology and are progressive; and ultimately affect both intellectual and motor functions. Children affected by MLD display progressive neurologic symptoms, including ataxia, seizures, and quadriplegia, culminating in severe disability and early death. MLD diagnosis is often delayed or missed. The true incidence rate of MLD is unknown but is estimated to be between 1 in 40,000 and 1 in 160,000 live births. We have initiated a prospective newborn screening study with implementation of MLD into the current newborn screening panel (covering 15 different diseases) for all newborns in the German states of Hamburg, Bremen, Schleswig-Holstein and Northern Lower Saxony. The total birth rate in this area is approximately 55,000 live births per year. A tiered screening approach is being applied where sulfatides levels are measured in dried blood spots, followed by ARSA activity and finally genetic confirmatory testing (ARSA, SUMF1, and PSAP genes). For the initial validation, 200-300 samples are being analyzed to establish all necessary assay performance characteristics. Cut-off determination for primary diagnostics will be established in a pre-pilot study with circa 5000 samples. Planned study duration is an initial 12 months with extension for another one to two years. 

SARS-CoV-2 infection presents a higher risk of morbidity and mortality in patients with chronic diseases. The care of patients with rare diseases, needed to be adapted after the start of the pandemic. Among the IEM, Mucopolysaccharidoses (MPS), Fabry Disease and Gaucher Disease are examples that also require frequent hospital visits for enzymatic replacement therapy (ERT) weekly or biweekly. Due to the pandemic, many infusions had to be reallocated to the patients' cities of origin or had their doses adjusted to reduce hospital exposure. Thinking about how to communicate simply the new flowchart of care and treatment, in addition to addressing general issues regarding the pandemic, our group created 'Beto and the Coronavirus' information booklet for patients.

To report the creation of simple and playful educational material on the main care that a patient with a rare disease should have both at home and in the hospital.

The booklet was developed from the 'Flowchart of therapeutic decision for patients with the lysosomal disease (DL) during the COVD-19 pandemic of the Brazilian Society of Medical Genetics and Genomics". The illustrations were made by our team. The dissemination took place through the Instituto Genética para Todos, having been translated into 3 languages.

The booklet made it possible to understand the new service and treatment flowcharts thoroughly. It also allowed it to be discussed with younger patients the role of personal protective equipment by both the team and the patient himself. The main character, Beto, also has MPS and needs to make ERT which generates a greater identification of patients with the booklet.

The pandemic has brought about wide-ranging modifications, including the treatment and follow-up of patients with rare diseases. Clear, simple, and playful communication allows for a greater understanding of the current situation.

Brazil Introduction Gaucher Disease (GD) is caused by deficient activity of GBA-coded lysosomal glucocerebrosidase