Methylmalonyl Coenzyme A (CoA) Epimerase Deficiency, an Ultra-Rare Cause of Isolated Methylmalonic Aciduria With Predominant Neurological Features.

Methylmalonyl coenzyme A (CoA) epimerase (MCE) converts D-methylmalonyl-CoA into L-methylmalonyl CoA in the final common degradation pathway of valine, isoleucine, methionine, threonine, odd-chain fatty acids, and cholesterol side chains. Methylmalonyl-CoA epimerase deficiency is an ultra-rare autosomal recessive disorder where methylmalonic acid, methylcitrate, 3-hydroxypropionate, and propionylcarnitine are accumulated. We describe two novel pediatric patients and review the previously reported cases of MCE deficiency. Including our two novel patients, at least 24 cases of MCE deficiency have been described, with a broad clinical spectrum ranging from asymptomatic to severely neurologically impaired patients. Our patients are siblings of Arabic origin who presented with metabolic decompensation with coma and epilepsy during infancy. Methylmalonic aciduria was disclosed, L-methylmalonyl-CoA mutase deficiency was assumed, and they were treated accordingly. When first seen in our country, aged 10 and four years, respectively, both presented severe intellectual disability and spasticity. The younger had an ataxic gait, and the older was wheelchair-ridden. The study of the MMUT, MMAA, MMAB, and MMADHC genes was normal. Subsequently, the pathogenic variant c.139C>T (p.Arg47*) in the MCEE gene was identified in homozygosity in both patients, leading to the diagnosis of MCE deficiency (Online Mendelian Inheritance in Man (OMIM®) 251120, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, MD, USA). Most patients were homozygous for that variant (83% of the alleles). Correct diagnosis allowed treatment adequacy and genetic counseling. Methylmalonyl-CoA epimerase deficiency shares a similar biochemical profile with other rare genetic disorders. Patients present with overlapping clinical features with predominant neurological manifestations; genetic testing is indispensable for diagnosis. We found no association between genotype and biochemical and clinical phenotypes.

Severe Influenza Virus and Respiratory Syncytial Virus Infections in Intensive Care Over the Last 15 Years.

INTRODUCTION: Influenza virus is a common agent of pediatric infections. Most cases are mild, but severe illness and death can occur. We aimed to analyze severe cases associated the influenza virus and compare it with respiratory syncytial virus (RSV). METHODS: This is a retrospective study of 0-17-year-old patients admitted to the intensive care unit (ICU) of Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra (Pediatric Hospital, Coimbra Hospital and University Center), a tertiary pediatric hospital in Coimbra, Portugal, over the last 15 years (2008-2022) due to influenza virus infection. Clinical presentation, severity, and evolution were analyzed. A comparison of children with RSV infection admitted in the same period was performed. RESULTS: We identified 47 cases of influenza virus infection (34% coinfection with other viruses), median age of 2.3 years (interquartile range (IQR) 6.1), and 38% had comorbidities. The median admissions were three/year (maximum 11 in 2019). Influenza A was identified in 96%. Ninety-six percent had respiratory symptoms, 38% had neurologic symptoms, and 28% had sepsis. The main reason for admission was respiratory failure (68%). The mean pediatric index of mortality 2 (PIM2) at admission was 9±15.9%. Ventilatory support was necessary in 66%, vasoactive support in 19%, and blood products in 17%. The median length of stay was four days (IQR 5). There were four (8.5%) deaths. During the same study period, there were 171 RSV-related admissions. When comparing influenza (group A, without RSV coinfection) and RSV (group B), the first had a higher PIM2 on admission, greater need of ventilatory support, more complications, and higher mortality (p=0.001). CONCLUSIONS: The number of influenza virus infections admitted to ICU was much lower than RSV. However, influenza was more severe and associated with all deaths registered.

A Hemoglobin Variant Causing an Unexplained Low Oxygen Saturation by Pulse Oximetry: Two Case Reports.

Pulse oximetry is now routinely used in neonatal resuscitation and for neonatal screening for congenital heart diseases. Beyond respiratory and cardiac diseases, hemoglobin (Hb) variants must be included in the differential diagnosis of low oxygen saturation detected by pulse oximetry. We aim to describe two cases of fetal Hb variant (heterozygous γ-globin gene (HBG1) mutation in exon 2 c.202G>A (p.Val68Met)), which was identified in two unrelated newborns.

Prospective study of loss of health-related quality adjusted life years in children and their families due to uncomplicated and hospitalised varicella.

INTRODUCTION AND AIMS: Although usually benign, varicella can lead to serious complications and sometimes long-term sequelae. Vaccines are safe and effective but not yet included in immunisation programmes in many countries. We aimed to quantify the impact on health-related quality of life (HRQoL) in terms of quality-adjusted life years (QALY) in children with varicella and their families, key to assessing cost-utility in countries with low mortality due to this infection. METHODS: Children with varicella in the community and admitted to hospitals in Portugal were included over 18 months from January 2019. Children's and carers' HRQoL losses were assessed prospectively using standard multi-attribute utility instruments for measuring HRQoL (EQ-5D and CHU9D), from presentation to recovery, allowing the calculation of QALYs. RESULTS: Among 109 families with children with varicella recruited from attendees at a pediatric emergency service (community arm), the mean HRQoL loss/child was 2.0 days (95 % CI 1.9-2.2, n = 101) (mean 5.4 QALYs/1000 children (95 % CI 5.3-6.1) and 1.3 days/primary carer (95 % CI 1.2-1.6, n = 103) (mean 3.6 QALYs /1000 carers (95 % CI 3.4-4.4). Among 114 families with children admitted to hospital because of severe varicella or a complication (hospital arm), the mean HRQoL loss/child was 9.8 days (95 % CI 9.4-10.6, n = 114) (mean 26.8 QALYs /1000 children (95 % CI 25.8-29.0) and 8.5 days/primary carer (95 % CI 7.4-9.6, n = 114) (mean 23.4 QALYs/1000 carers (95 % CI 20.3-26.2). Mean QALY losses/1000 patients were particularly high for bone and joint infections [67.5 (95 % CI 43.9-97.6)]. Estimates for children's QALYs lost using the CHU9D tool were well correlated with those obtained using EQ-5D, but substantially lower. CONCLUSIONS: The impact of varicella on HRQoL is substantial. We report the first measurements of QALYs lost in hospitalised children and in the families of children both in the community and admitted to hospital, providing important information to guide vaccination policy recommendations.