Safety of COVID-19 vaccines in children with inborn errors of metabolism in terms of developing metabolic decompensation.

AIM: There are no recommended guidelines or clinical studies on safety of COVID-19 vaccines in patients with inborn errors of metabolism (IEMs). Here, we aimed to examine the relationship between COVID-19 vaccination and metabolic outcome in paediatric IEM patients. METHODS: Patients with IEM between the ages of 12 and 18 were enrolled. Term metabolic decompensation was defined as acute disruption in metabolic homeostasis due to vaccination. Clinical and biochemical markers were compared between pre- and post-vaccination periods. RESULTS: Data from a total of 36 vaccination episodes in 18 patients were included. Thirteen patients had intoxication-type metabolic disorders including organic acidemia (OA), urea cycle disorders (UCDs), maple syrup urine disease (MSUD) and phenylketonuria (PKU); 4 patients had energy metabolism disorders including fatty acid metabolism disorders and LIPIN 1 deficiency; and 1 patient had glycogen storage disorder (GSD) type 5. Seventeen patients received BNT162b2, and 1 received CoronaVac because of an underlying long QT syndrome. Fatty acid metabolism disorders, LIPIN 1 deficiency and GSD type 5 were included in the same group named 'metabolic myopathies'. In two PKU patients, plasma phenylalanine level increased significantly within 24 h following the second dose of vaccination. None of the OA, UCD, MSUD and metabolic myopathy patients experienced acute metabolic attack and had emergency department admission due to metabolic decompensation within 1 month after vaccination. CONCLUSIONS: COVID-19 vaccines did not cause acute metabolic decompensation in a cohort of 18 children with IEM.

Altered immune response in organic acidemia.

BACKGROUND: Most patients with organic acidemia suffer from recurrent infections. Although neutropenia has been reported in multiple studies, other components of the immune system have not been evaluated thoroughly. This study was conducted to assess the immune status of patients with organic acidemia (OA). METHODS: Thirty-three patients with OA who were followed up in Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Nutrition and Metabolism Department and a total of 32 age- and sex-matched healthy controls were enrolled to the study. The demographic and clinical data were recorded retrospectively from patient files. Complete blood counts, immunoglobulins, and lymphocyte immunophenotyping were recorded prospectively in a symptom- (infection-) free period. RESULTS: Of the 33 patients enrolled to the study, 21 (88%) were diagnosed with methylmalonic acidemia, 10 (33%) with propionic acidemia, and two (6.6%) with isovaleric acidemia. The mean age of the patients with OA and healthy subjects were 5.89 ± 4.11 years and 5.34 ± 4.36, respectively (P = 0.602). Twenty-nine (88%) of the patients had experienced frequent hospital admission, 13 (39%) were admitted to pediatric intensive care unit, and 18 (55%) suffered from sepsis. Naïve helper T cells and recent thymic emigrants were significantly lower in OAs (P < 0.001). Various defects in humoral immunity have also been documented including memory B cells and immunoglobulins. CONCLUSIONS: Patients with OAs may show adaptive immune defects rendering them susceptible to infections. Metabolic reprogramming based on nutritional modifications may be a promising therapeutic option in the future.

The Impact of Telemedicine for Monitoring and Treatment of Phenylketonuria Patients on Metabolic Outcome During Coronavirus Disease-19 Outbreak.

Introduction: The prognosis of phenylketonuria (PKU) in terms of neurocognitive outcome is directly related to lifelong phenylalanine (Phe) levels and adherence to treatment. Monitoring and treatment of PKU patients can be complicated in challenging circumstances as pandemics. This study aims to evaluate the impact of telemedicine for monitoring and treatment of PKU patients on metabolic outcome during coronavirus disease-19 (COVID-19) outbreak. Materials and Methods: Patients who were diagnosed as PKU and treated with low Phe diet, tetrahydrobiopterin (BH4), or BH4 adjunct with low Phe diet were enrolled. Study period was divided into two periods: prepandemic period wherein patients were followed up in outpatients' clinic and during pandemic wherein telemedicine was used. Demographic findings, laboratory results, and therapy responses were reviewed retrospectively and compared between the two periods. All procedures were in accordance with the ethical standards of the local ethical committee of Cerrahpasa Medical Faculty (17/11/2020-151640) and with the Helsinki Declaration of 1975, as revised in 2013. Results: Ninety-three (n = 93) patients were enrolled to this study. The ratio of the samples with Phe levels in the recommended ranges was found to be statistically higher during the pandemic wherein an online monitoring system was used in all treatment modalities (p< 0.05). The decrease in Phe washout frequency was statistically significant during the pandemic in the low Phe diet group (p < 0.05). Considering the relationship between Phe tolerance before and during the pandemic, a significant increase in Phe tolerance was noted during the pandemic in the low Phe diet group (p< 0.05). Conclusions: Telemedicine can be an appropriate and effective monitoring option for PKU patients during the COVID-19 pandemic.

Inborn errors of metabolism and coronavirus disease 2019: Evaluation of the metabolic outcome.

BACKGROUND: Infectious diseases can result in a catabolic state and possibly trigger an acute metabolic decompensation in inborn errors of metabolism (IEM), which could be life threatening. Studies regarding the course of severe acute respiratory syndrome coronavirus 2 infections in patients with IEM are generally limited to case reports. Here, we aimed to evaluate the clinical findings of coronavirus disease 2019 (COVID-19) and describe the impact of severe acute respiratory syndrome coronavirus 2 infections on metabolic outcomes in IEM patients. METHODS: Patients who were diagnosed with different types of IEM and developed microbiologically confirmed COVID-19 infection were included. Clinical findings and laboratory results were recorded retrospectively in terms of both IEM and COVID-19. RESULTS: Eleven patients with diagnosis of intoxication type metabolic disorders, five patients with energy metabolism disorders, and six patients with complex molecular disorders were enrolled. The most frequent clinical finding was fever (52.1%) followed by fatigue/myalgia (47.8%). None of the patients was younger than 1 year. None of the patients presented severe or critical disease. In terms of metabolic decompensation, two patients diagnosed with propionic acidemia, one patient with methylmalonic acidemia and one patient with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency presented clinical and biochemical findings of an acute metabolic attack. CONCLUSIONS: Based on our results, IEM are not found to be an additional risk factor for severe COVID-19 infection. However, patients with intoxication type and energy metabolism disorders should be considered as a vulnerable population for COVID-19 and have a major risk of developing acute metabolic decompensation that can lead to life-threatening complications.

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

Introduction: SARS-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. Methods: Fifteen 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. Results: Anti-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. Discussion: Humoral 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.

Telemedicine Applications in a Tertiary Pediatric Hospital in Turkey During COVID-19 Pandemic.

Background: A novel type of Coronavirus emerged at Wuhan in late 2019 involving preferentially the respiratory system. Owing to the rapid spread, almost 22 million people became infected and 700,000 died. Similar to other countries, the need for additional hospital beds and intensive care units required diversion of health care resources toward the care for those with COVID-19 in Turkey. Telemedicine appeared as a safe and low-cost alternative for the maintainability of pediatric health services during the pandemics. Within this context, we aimed to deliver the health services through telemedicine during the follow-up of chronic childhood diseases. Materials and Methods: This prospective study included five pediatric subspecialties, including allergy immunology, hematology and oncology, nephrology, rheumatology, and inborn metabolic disorders. After the interview, patients and involved physicians were requested to fill out a questionnaire designed to measure the level of satisfaction and the quality of the service we offered. Results: Of the 263 interviews, overall patient and physician satisfaction was 99% and 87%, respectively. As results of the interviews, 250 routine visits were performed, 181 acute complaints were assessed, drug changes were made in 118 patients, 9 patients were determined to be unable to get their drugs, and 12 who misused their drugs. The main advantage of the telemedicine declared by the patients was "not to waste time for transportation." The main concerns of the participants were inability to perform physical and laboratory examinations. Conclusion: Consequently, we considered telemedicine as a feasible alternative not only during pandemics but also in daily practice in Turkey.

Challenges of following patients with inherited metabolic diseases during the COVID-19 outbreak. A cross-sectional online survey study.

OBJECTIVES: There has been a recent worldwide outbreak of coronavirus disease (COVID-19). Most of the health system capacity has been directed to COVID-19 patients, and routine outpatient clinics have been suspended. Chronic disease patients, such as inherited metabolic disorders (IMD), have had trouble accessing healthcare services. METHODS: An online cross-sectional survey was conducted among patients with IMDs who were present for a follow-up at our clinic to address their problems during pandemic period. Our clinic's Instagram and Facebook accounts were used to invite the participants. Three reminders were given between May 1, 2020, and May 30, 2020. Survey questions were analyzed using descriptive statics. RESULTS: A total of 213 patients completed our survey. Incomplete surveys were excluded, and 175 questionnaires were evaluated. Most of patients had a special diet, and 51% of them had some difficulty with their diet. The reported rate of using a special treatment was 38%, and most of these patients (91%) had no problem receiving these special therapies during this time. Parents who were wearing masks while caring for their child were very few (17%), but a vast majority of parents (73.7%) had high handwashing rates. None of the patients had a SARS-COV2 infection until this paper was written. CONCLUSION: This is the first study that aims to determine the problems faced by patients with IMD during the COVID-19 period. Considering that the pandemic will not immediately pass, recognizing the problems faced by patients with chronic diseases and developing solutions would help these patients avoid long-term damage.

Childhood-onset Takayasu arteritis: A 15-year experience from a tertiary referral center.

AIM: To describe clinical manifestations, angiographic findings, treatment, activity and damage of our Takayasu arteritis patients. METHOD: The patients who met European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society classification criteria for childhood-onset Takayasu arteritis were reviewed in a retrospective longitudinal manner from 2002 to 2017. Extent of the disease was assessed by Disease Extent Index for Takayasu Arteritis (DEI.Tak), activity by Pediatric Vasculitis Activity Score and Indian Takayasu's Arteritis Activity Score (ITAS 2010) and damage by Pediatric Vasculitis Damage Index and Takayasu Arteritis Damage Score (TADS). RESULTS: Sixteen subjects (75% female) with a median disease duration of 3.1 years were enrolled in this study. While the median age at disease onset was 12.1 years, there was only a 2.5 months diagnostic delay. Treatment regime included corticosteroids (100%), which were combined with azathioprine or methotrexate in 93.8% and 37.5% of the subjects, respectively. Severe and refractory cases were treated with cyclophosphamide (62.5%) and subsequently with tocilizumab (37.5%). Seven patients (43.8%) required either percutaneous endovascular intervention or bypass for severe disease refractory to medications. The correlation of the activity and damage scores with each other was fairly good. Damage was found to be associated only with high disease activity and extensive disease at disease onset, but not with other parameters. CONCLUSION: Despite high usage rates of aggressive immunosuppressive therapy and biologic agents, almost half of the patients underwent interventional procedures. When medications failed, endovascular and surgical interventions were of great importance to avoid end-organ ischemia. The performance of the new activity (DEI.Tak and ITAS2010) and damage indices (TADS) seems satisfactory.