BNT162b2 COVID-19 vaccination elicited protective robust immune responses in pediatric patients with inborn errors of metabolism

IntroductionSARS-CoV-2 infection can lead to a life-threatening acute metabolic decompensation in children with inborn errors of metabolism (IEM), so vaccination is mandatory. However, IEMs can also impair innate or adaptive immunity, and the impact of these immune system alterations on immunogenicity and vaccine efficacy is still unknown. Here, we investigated humoral immune responses to the BNT162b2 mRNA COVID-19 vaccine and clinical outcomes in pediatric IEM patients.MethodsFifteen patients between 12-18 years of age with a confirmed diagnosis of IEM, and received BNT162b2 were enrolled to the study. Patients with an anti-SARS-CoV-2 IgG concentration >50 AU/mL before vaccination were defined as “COVID-19 recovered” whereas patients with undetectable anti-SARS-CoV-2 IgG concentration were defined as “COVID-19 naïve”. Anti-SARS-CoV-2 Immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibody (nAb) titers were measured to assess humoral immune response.ResultsAnti-SARS-CoV-2 IgG titers and nAb IH% increased significantly after the first dose. The increase in antibody titers after first and second vaccination remained significant in COVID-19 naïve patients. Complete anti-SARS-CoV-2 IgG seropositivity and nAb IH% positivity was observed in all patients after the second dose. Vaccination appears to be clinically effective in IEM patients, as none of the patients had COVID-19 infection within six months of the last vaccination.DiscussionHumoral immune response after two doses of BNT162b2 in pediatric IEM patients was adequate and the immune response was not different from that of healthy individuals

COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1

Objectives: The impact of coronavirus disease-19 (COVID-19) on metabolic outcome in patients with inborn errors of metabolism has rarely been discussed. Herein, we report a case with an acute encephalopathic crisis at the course of COVID-19 disease as the first sign of glutaric aciduria type 1 (GA-1). Case presentation: A 9-month-old patient was admitted with encephalopathy and acute loss of acquired motor skills during the course of COVID-19 disease. She had lethargy, hypotonia, and choreoathetoid movements. In terms of COVID-19 encephalopathy, the reverse transcriptionpolymerase chain reaction assay test for COVID-19 was negative in cerebral spinal fluid. Brain imaging showed frontotemporal atrophy, bilateral subcortical and periventricular white matter, basal ganglia, and thalamic involvement. Elevated glutarylcarnitine in plasma and urinary excretion of glutaric and 3-OH-glutaric acids was noted. A homozygote mutation in the glutaryl-CoA dehydrogenase gene led to the diagnosis of GA-1. Conclusions: With this report, neurological damage associated with COVID-19 has been reported in GA-1 patients for the first time in literature

Impact of sodium phenylbutyrate treatment in acute management of maple syrup urine disease attacks: a single-center experience

Objectives: Accurate management of metabolic decompensation in maple syrup urine disease (MSUD) has a crucial role, as acute attacks can cause neurological sequels and can be life threatening. Here, we aimed to evaluate effect of sodium phenylbutyrate (NaPBA) in acute management of MSUD attacks

Coagulation Disturbances in Patients with Argininemia

BACKGROUND Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. METHODS In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. RESULTS All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. CONCLUSIONS Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms

Treatment of maple syrup urine disease with high flow hemodialysis in a neonate

Continious renal replacement therapy (CRRT) is a well recognizied treatment of choice in acute renal failure, however CRRT became a preferred treatment of metabolic emergencies with high leucine and ammonia levels like Maple syrup urine disease (MSUD). MSUD is a rare metabolic disorder caused by deficiency in the activity of the branched-chain a-ketoacid dehydrogenase complex. The toxic accumulation of branched chain amino acids during acute metabolic decompensation is associated with the appearance of permanent neurological symptoms. Four patients were admitted to our pediatric intensive care department with complains of poor feeding, vomitting, irratibility and coma. Physical examination of the neonates were similar having stupor, hypotonia and depressed newborn reflexes. The leucine levels were between 930-4400 mu mol/L. The diagnosis of MSUD was confirmed in all four. They were treated successfully with high flow CRRT having the rates were between 4120 ml/h/1.73m2 and 9830 ml/h/1.73m2. Early treatment is essential to prevent neurotoxicity and death. CRRT is a choice of treatment in metabolic crisis of MSUD. Herein, we report the successful treatment of acute metabolic decompensation of MSUD with CRRT in 4 neonates

Continuous Renal Replacement Therapy with High Flow Rate Can Effectively, Safely, and Quickly Reduce Plasma Ammonia and Leucine Levels in Children

Introduction: Peritoneal dialysis and continuous renal replacement therapy (CRRT) are the most frequently used treatment modalities for acute kidney injury. CRRT is currently being used for the treatment of several non-renal indications, such as congenital metabolic diseases. CRRT can efficiently remove toxic metabolites and reverse the neurological symptoms quickly. However, there is not enough data for CRRT in children with metabolic diseases. Therefore, we aimed a retrospective study to describe the use of CRRT in metabolic diseases and its associated efficacy, complications, and outcomes. Materials and Methods: We performed a retrospective analysis of the records of all patients admitted in the pediatric intensive care unit (PICU) for CRRT treatment. Results: Between December 2014 and November 2018, 97 patients were eligible for the present study. The age distribution was between 2 days and 17 years, with a mean of 3.77 ± 4.71 years. There were 13 (36.1%) newborn with metabolic diseases. The patients were divided into two groups: CRRT for metabolic diseases and others. There was a significant relationship between the groups, including age (p ≤ 0.001), weight (p = 0.028), blood flow rate (p ≤ 0.001); dialysate rate (p ≤ 0.001), and replacement rate (p ≤ 0.001). The leucine reduction rate was 3.88 ± 3.65 (% per hour). The ammonia reduction rate was 4.94 ± 5.05 in the urea cycle disorder group and 5.02 ± 4.54 in the organic acidemia group. The overall survival rate was 88.9% in metabolic diseases with CRRT. Conclusion: In particularly hemodynamically unstable patients, CRRT can effectively and quickly reduce plasma ammonia and leucine