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

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

Postural tremor in L-2-hydroxyglutaric aciduria is associated with cerebellar atrophy

Objective In this study, we performed analysis of brainstem reflexes and movement disorders using surface polymyogram in L-2-hydroxyglutaric aciduria (L2HGA). We also reviewed all cases in the literature with detailed clinical and radiological description to analyze the anatomical correlates of involuntary movements. Patients and method We performed surface electromyography of appropriate muscles, long-loop reflexes, and somatosensory evoked potentials and analyzed the neuroimaging findings in patients with L2HGA and recorded blink reflex (BR), auditory startle response (ASR), and startle response after somatosensory stimuli (SSS) in patients and healthy subjects. We also performed a systematic literature search to identify the association of neuroimaging findings and movements disorders in previous patients with L2HGA. Results Thirteen patients were enrolled in the study. Among them, ten had low-amplitude postural tremor with a frequency between 4 and 7 Hz. The tremor was predominant on distal parts of the upper extremities. Postural tremor was accompanied by negative myoclonus in one-third. The BR, ASR, and SSS, all, were hypoactive. There was a close association of postural tremor with cerebellar atrophy in patients who participated in this study and by the analysis of the previously reported patients. Conclusions Low-amplitude postural tremor is common in L2HGA. It is related with cerebellar atrophy. Although the neuroimaging shows no overt lesions at the brainstem, there is a functional inhibition at this level

Adrenal steroids reference ranges in infancy determined by LC-MS/MS

© 2021, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.Background: Interpretation of the results of steroid hormone measurements is challenging at early infancy. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method provides a powerful tool for diagnosing steroidogenesis disorders. We aimed to develop normative data for a 14-steroid panel and four adrenal enzyme activity indices, determined by LC-MS/MS from 3 days to 6 months of age. Methods: Age- and sex-specific plasma steroid concentrations were calculated in 324 healthy full-term neonates and infants (151 females). Percentile curves were devised. Steroid ratios were evaluated as biomarkers of adrenal enzyme activities. The steroid profiles of four patients with adrenal enzyme deficiencies were included to test the diagnostic efficiency. Results: Nine steroids showed age, but none showed sex specificity. The concentrations of progestins and androgens were higher at 7–14 days than at 3–7 days. After the first month, adrenal androgen concentrations decreased significantly. Adrenal enzyme activities changed towards increasing cortisol over the first 6 months. There were several-fold differences in diagnostic steroids and related adrenal enzyme activity indices between the patients and the healthy group. Conclusions: The majority of adrenal steroids show age-related variations in the neonatal period and early infancy. Our data will enable accurate interpretation of steroid measurements for etiologic diagnosis of disorders of steroidogenesis. Impact: LC-MS/MS method is capable of quantitating numerous analytes simultaneously, which provides an integrated picture of adrenal steroidogenesis in a small amount of sample.The development of LC-MS/MS-based normative data of steroid hormones in healthy infants is crucial to differentiate physiologic alterations from steroidogenic defects during the first 3–6 months of infancy.Previous studies had limitations due to the small numbers of samples available by sex and by age groups.Our detailed normative data and percentile curves will enable accurate interpretation of steroid measurements for etiologic diagnosis of disorders of steroidogenesis without the need for further invasive testing

Evaluation of the effect of chenodeoxycholic acid treatment skeletal system findings in patients with cerebrotendinous xanthomatosis

Aim: The primary purpose of the present study is to evaluate the effect of chenodeoxycholic acid treatment on skeletal system findings in patients with cerebrotendinous xanthomatosis

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

Background: 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

Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency

Abstract Background Congenital sphingosine-1-phosphate (S1P) lyase deficiency due to biallelic mutations in SGPL1 gene has recently been described in association with primary adrenal insufficiency and steroid-resistant nephrotic syndrome. S1P lyase, on the other hand, is therapeutically inhibited by fingolimod which is an oral drug for relapsing multiple sclerosis (MS). Effects of this treatment on adrenal function has not yet been evaluated. We aimed to test adrenal function of MS patients receiving long-term fingolimod treatment. Methods Nineteen patients (14 women) with MS receiving oral fingolimod (Gilenya®, Novartis) therapy were included. Median age was 34.2 years (range; 21.3–44.6 years). Median duration of fingolimod treatment was 32 months (range; 6–52 months) at a dose of 0.5 mg/day. Basal and ACTH-stimulated adrenal steroid measurements were evaluated simultaneously employing LC-MS/MS based steroid panel. Basal steroid concentrations were also compared to that of sex- and age-matched healthy subjects. Cortisol and 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone were used to assess glucocorticoid, mineralocorticoid and sex steroid producing pathways, respectively. Results Basal ACTH concentrations of the patients were 20.8 pg/mL (6.8–37.8 pg/mL) (normal range; 5–65 pg/mL). There was no significant difference in the basal concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone between patients and controls (p = 0.11, 0.058, 0.74, 0.15; respectively). All patients showed adequate cortisol response to 250 mcg IV ACTH stimulation (243 ng/mL, range; 197–362 ng/mL). There was no significant correlation between duration of fingolimod treatment and basal or ACTH-stimulated cortisol or change in cortisol concentrations during ACTH stimulation test (p = 0.57, 0.66 and 0.21, respectively). Conclusion Modification and inhibition of S1P lyase activity by the long-term therapeutic use of fingolimod is not associated with adrenal insufficiency in adult patients with MS. This suggests that S1P lyase has potentially a critical role on adrenal development rather than the function of a fully mature adrenal gland

Evaluation of clinical, neuroradiologic, and genotypic features of patients with L-2-hydroxyglutaric aciduria

Aim: L-2-hydroxyglutaric aciduria is a slowly progressive neurometabolic disorder caused by an enzymatic deficiency of L-2-hydroxyglutarate dehydrogenase. Here, we aimed to evaluate the clinical, neuroradiologic, and genotypic characteristics of patients with L-2-hydroxyglutaric aciduria who were followed in our outpatient clinic