IgA vasculitis (IgAV) is the most common childhood vasculitis. The main cause of morbidity and mortality in children with IgAV is nephritis (IgAVN), but the risk of its development, severity, and chronicity remain unclear. Erythrocyte glutathione S-transferase (e-GST) activity has been previously detected as a sensitive marker of kidney function impairment in several diseases. We spectrophotometrically assessed and correlated e-GST activity between 55 IgAV patients without nephritis (IgAVwN), 42 IgAVN patients, and 52 healthy controls. At disease onset, e-GST activity was significantly higher in IgAVN patients (median (interquartile range)) (5.7 U/gHb (4.4–7.5)) than in IgAVwN patients (3.1 U/gHb (2.2–4.2); p < 0.001), and controls (3.1 U/gHb (1.9–4.2); p < 0.001). Therewithal, there were no differences between the IgAVwN patients and controls (p = 0.837). e-GST activity was also significantly higher in the IgAVN patients than in the IgAVwN patients after 3 months (5.0 U/gHb (4.2–6.2) vs. 3.3 U/gHb (2.3–4.1); p < 0.001) and 6 months (4.2 U/gHb (3.2–5.8) vs. 3.3 U/gHb (2.1–4.1); p < 0.001) since the disease onset. Consistent correlations between e-GST activity and serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria levels were not detected. In conclusion, increased e-GST activity can serve as a subtle indicator of kidney function impairment in children with IgAV.

Because of the unpredictable efficacy of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA), the possibility of a favourable outcome is reduced in more than 30% of patients. To investigate the possible influence of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene deletion polymorphisms on MTX efficacy in patients with JIA, we determined these polymorphisms in 63 patients with JIA who did not achieve remission and 46 patients with JIA who achieved remission during MTX therapy. No significant differences were observed in the distribution of single GSTM1 or GSTT1 deletion polymorphisms or their combination between the two groups: 58.7% to 63.5%; p = 0.567, 17.4% to 22.2%; p = 0.502, and 13% to 12.7%; p = 0.966, respectively. Our results suggest that GSTM1 and GSTT1 deletion polymorphisms do not influence the efficacy of MTX in patients with JIA. Additional studies are required to determine the possible influence of GST deletion polymorphisms on MTX efficacy in patients with JIA.

Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.

Asparagine synthetase deficiency (ASNSD) is a rare metabolic disease causing congenital microcephaly, severe developmental delay, and spastic quadriplegia. Although the central nervous system is severely affected, other organ systems appear unaffected by asparagine deficiency. We present an infant homozygous for the mutation c.904‐1G>A in the ASNS gene, whose clinical presentation and radiological findings were typical for ASNSD. Following the patient's death at the age of 6 months, histological and immunohistochemical examination of the telencephalon revealed a vast disturbance of migration of neuronal subpopulations, consequently severe disorganization of cortical layers, and thinning of the cerebral cortex. These findings provide novel insights into disease pathogenesis and may explain the hallmark features of ASNSD, including microcephaly and epilepsy.

Introduction Corticosteroid therapy can lead to severe iatrogenic adrenal insufficiency (IAI) and Cushing syndrome. These side-effects are common with systematic corticosteroid treatment and are less common with topical treatment modalities, even though it has been described with corticosteroid inhalation, trans- or intradermal use, intranasal and intraarticular corticosteroid application. Although ocular administration was thought to rarely lead to the development of IAI, recent studies have shown that more than two-thirds of children develop some degree of adrenal suppression, and patients who have developed an adrenal crisis during anaesthesia have been described. Case Report We present a female infant who developed postoperative glaucoma following the surgery for congenital cataract. The therapy with topical corticosteroid eye preparations was started at the age of 5.5 months [Maxitrol drops (dexamethasone 0,1%), Tobradex ointment (dexamethasone 1 mg/g)], at an average dose of 1.5 mg/day dexamethasone. At the age of 8.7 months, 3 months after the initiation of corticosteroid use, she was examined by a paediatric endocrinologist for growth retardation [BW 6190 g (<3 ct, -2.1 SDS), BH 63 cm (<3 ct, -2.4 SDS)]. There were no other clinical signs of Cushing syndrome or other growth hormone deficiency associated syndromes. Laboratory finding revealed low ACTH levels with suppressed cortisol secretion (ACTH 1,1 pmol/L; norm 1,6-13,9; cortisol <3 nmol/lL, norm 138-690). Further investigation ruled out other endocrine causes of reduced growth and congenital malformations of other organ systems. A normal female karyotype was found by classical karyotyping, 46, XX. Analysis of a panel of genes whose mutations are associated with congenital cataracts found no pathogenic variants. The girl was of normal intellectual development, and the result of pharmacogenetic analysis showed normal metabolism of corticosteroid drugs. Despite the recommendation to gradually reduce the dose of corticosteroids, local therapy was abruptly discontinued and at the age of 9 months the girl was hospitalized due to the development of an adrenal crisis. Hydrocortisone replacement therapy was initiated (10 mg/m2/day) and topical ocular corticosteroids (dexamethasone 0,1%) were continued in the dose of 2-5 drops daily. Adrenal function recovered after 10 months (ACTH short test 250 µg/m2; cortisol 60’ 523,7 nmol/L), followed by growth spurt. At the age of 3 years and 4 months, the girl reached 25-50 centile in high-for-age curve (-0.15 SDS) which is in accordance with her genetic potential (mother’s height 159.5 cm, father’s height 176 cm, mid parental height 162.5 cm) Conclusion Topical ocular administration of corticosteroid preparations, although rarely, may lead to the development of IAI. Growth suppression due to corticosteroid administration may occur in children without other symptoms of Cushing syndrome. Growth monitoring is required in all children receiving long-term topical corticosteroid therapy, and discontinuation of therapy should be gradual due to the possibility of developing of an adrenal crisis.