Insights Into the COVID-19 Infection Related to Inherited Metabolic Diseases

Introduction

Inherited metabolic diseases (IMDs)also known as inborn errors of metabolism (IEMs), are a group of disorders which result from the deficiency or the abnormality of an enzyme, its cofactor or a transporter(Figure 1), resulting in accumulation of a substrate or the deficiency of the product (J V Leonard & Morris, 2000; Saudubray, Sedel, & Walter, 2006).Although IMDs are individually rare, they are collectively common, with an overall incidence of more than 1:1000(Campeau, Scriver, & Mitchell, 2008).The first description of these disorders was made by SirArchibald Garrod in 1902 (Garrod, 1902). Nowadays, there are estimated to be more than 1000 inborn errors of metabolism that have been recognized, with approximately 25% of them having manifestations in the neonatal period(Illsinger & Das, 2010; James V Leonard & Morris, 2006; Saudubray et al., 2006). The application of tandem mass spectrometry to newborn screening and prenatal diagnosis have enabled presymptomatic diagnosis for some IMDs, more than 300 “new” disorders were describedbetween 2011 and 2016, 85% presenting with predominantly neurologic manifestations(Fernandes, Saudubray, Van den Berghe, & Walter, 2006).Neonates with IMDs are usually healthy at birth with signs typically developing in hours to days after birth. The signs are usually nonspecific, and may include decreased activity, poor feeding, respiratory distress, lethargy or seizures. These signs are common to several other neonatal conditions, such as sepsis and cardiopulmonary dysfunction.Given their frequency and potential for treatment, the clinician should be aware of this group of conditions and learn to identify the typical manifestations of the different inborn errors of metabolism. The vast majority of IMDs are inherited in an autosomal recessive manner. Therefore, a history of parental consanguinity or a previously affected sibling should raise the suspicion of IMDs. Some IMDs, such as Mucopolysaccharidosis type II (MPS II), and Fabry disease, are X-linked. In X-linked disorder, typically male patients have severe diseases, whereas female patients are either asymptomatic or have milder disease due to X-chromosome inactivation.There has been significant progress for the diagnosis and treatment of IMDs especially during the last decade, early diagnosis is very important to preventmortality and morbidity in untreated cases (Raghuveer, Garg, & Graf, 2006).

Pathophysiologically, IMDs can be divided into three groups based on the substrate accumulated, the group of enzymes affected, and the organelle that has the defective pathway or the clinical presentation (Saudubray et al., 2006). The first includes IMDs causing intoxication that give rise to an acute or chronic intoxication because of defects in the intermediary metabolic pathway, resulting in the accumulation of toxic compounds proximal to the metabolic block; (e.g., Aminoacidopathies, Organic acidurias, Defects in carbohydrate metabolism, urea cycle disorders, sugar intolerances). The second group includes IMDs resulting in energy deficiency, such as mitochondrial respiratory chain defects, defects of Krebs cycle and Fatty acid oxidation defects. The third group is IMDs resulting in defects in the synthesis or the catabolism of complex molecules in certain cellular organelles, such as lysosomal storage disorders, Peroxisomal disorders, glycosylation, and cholesterol synthesis defects.Children and adults with an IMD are particularly at higher risk of morbidity and mortality when exposed to viral or bacterial infections due to their chronic preexisting conditions and potentially vulnerable immune system (McGuire, 2020; Parvaneh, Quartier, Rostami, Casanova, & de Lonlay, 2014).