SARS-CoV-2 infection in a patient with propionic acidemia

(2020) 15:306 Caciotti et al. Orphanet J Rare Dis https://doi.org/10.1186/s13023-020-01563-w Open Access LETTER TO THE EDITOR SARS‑CoV‑2 infection in a patient with propionic acidemia Anna Caciotti1, Elena Procopio2, Francesca Pochiero2, Silvia Falliano1, Giuseppe Indolfi3, Maria Alice Donati2, Lorenzo Ferri1, Renzo Guerrini1,4 and Amelia Morrone1,4* Abstract We describe a 14-month-old boy, with a previous diagnosis of propionic acidemia (PA) by expanded newborn screening, who, admitted for a suspected metabolic crisis, tested positive for SARS-CoV-2. Since propionic acidemia was diagnosed, the patient has followed the recommended diet for this inborn error of metabolism. Although propionic acidemia patients are at a high risk of suffering metabolic crises, frequently associated with permanent clinical complications, psychomotor development of this patient was normal. The SARS-CoV-2 infection (at about 1 year of age) caused the patient’s first metabolic crisis. However, his clinical course was in keeping with a mild clinical form of COVID-19, and he recovered without experiencing severe clinical consequences. We describe this patient in order to improve the knowledge about follow up of PA patients identified by newborn screening and to increase the limited number of reports of SARS-CoV-2 infection in children with comorbidities, especially inborn errors of metabolism. Keywords: Propionic academia, SARS-CoV-2, COVID-19, PCCB Background Propionic acidemia (PA) (MIM #606054) is a multisystemic inborn error of the catabolic pathway of branchedchain amino acids (isoleucine, valine, methionine and threonine). It is caused by mutations in the PCCA and PCCB genes, encoding alpha and beta subunits (UniProtKB—P05165 and P05166) of the mitochondrial enzyme propionyl-CoA carboxylase (PCC, EC 6.4.1.3) [1]. Biochemical characteristics include metabolic acidosis, ketosis, hyperammonaemia, altered glycemia, neutropenia, anemia and thrombocytopenia [1]. PA is characterised by high levels of 3-hydroxypropionate, methylcitrate, tiglylglycine and propionylglycine in urine [2]. In recent years, an increasing number of patients have been detected by newborn screening (NBS) programs which check for elevated levels of C3 *Correspondence: 1 Molecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children’s Hospital, Viale Pieraccini n. 24, 50139 Florence, Italy Full list of author information is available at the end of the article (propionyl carnitine) in dried blood spots (DBS) taken from 48 to 72 h after birth [3]. The altered catabolism of proteins in PA causes severe psychomotor impairment, seizures, movement disorders, gastrointestinal symptoms, cardiomyopathy, renal involvement, hematological abnormalities, osteoporosis, immune dysfunctions and other symptoms. Most affected patients present the severe neonatal form, although later onset and milder forms are described [4]. An acute metabolic decompensation, which can result in selective organ damage, especially brain injury, can be avoided with therapy [1] and controlled diet [5]. In managing PA patients, the key objective is to prevent acute episodes [5]. Acute decompensations, whose initial management is critical, can be triggered by fever, vomiting, prolonged fasting, gastroenteritis and other infections [5, 6]. The health gains of NBS for PA in overall outcome are modest, even if mortality in patients detected by NBS is lower than in the group detected by selected metabolic screening [3, 5–7]. © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Caciotti et al. Orphanet J Rare Dis (2020) 15:306 Page 2 of 5 The recent epidemic of the 2019 novel coronavirus SARS-CoV-2, has caused significant morbidity and mortality worldwide. In general, children appear to have a milder clinical course compared to adults [8–11]. Little is known about SARS-CoV-2 infection in children with comorbidities (such as congenital heart, lung and airway diseases, chronic heart and kidney diseases, malnutrition, tumors, diabetes, immunodeficiency or hypoimmunity) and little information is available on the effects of the infection in pediatric patients with congenital inborn errors of metabolism (IEM) [8, 12]. However, emerging guidelines have been proposed to manage eventual SARS-Co V2 infection in lysosomal diseases and on inherited heart diseases [13–15]. In addition, it has been reported that a patient affected by mucolipidosis type II died because of pneumonia complicated by acute respiratory distress syndrome (ARDS) [16]. Here we describe a 14-month-old patient followed by our team since PA was detected by NBS and confirmed by PCCA and PCCB gene sequencing, who was recently infected by SARS-CoV-2. Case report At birth all the patient’s growth and vital parameters were normal and his APGAR score was 9 1–105. PA was diagnosed by NBS 5 days after birth. Molecular analysis of the PA genes (PCCA and PCCB), performed by next generation sequencing procedures (Nextera Flex technology, Illumina), identified compound heterozygosity for two previously reported mutations in the PCCB gene, the NM_000532: c.337C > T p.(Arg113*) [17] and the c.1298dupA p.(Ala434Glyfs*7) [18]. Both mutations, each of which was present at the heterozygous status in one of the parents, cause premature stop codons, which are likely to prevent production of normal and functional PCCB proteins. On his fifth day of life, due to hyperammoniemia (357 μmol/L, n.v < 50) and metabolic acidosis, the child was admitted to our hospital. Protein intake was stopped and intravenous glucose and lipids, l-carnitine, N-Carbamylglutamate, sodium benzoate and arginine hydrochloride were administered (Table 1). 24 h after hospitalization, ammonemia levels were normal and natural proteins (human milk) were reintroduced. Therapy with ammonia scavengers was suspended on the 9th day after birth (Table 1). Transfontanellar ultrasoun (...truncated)