Erythrocyte Glutathione S-Transferase Activity as a Sensitive Marker of Kidney Function Impairment in Children with IgA Vasculitis.

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.

[Congenital hyperinsulinism--novel insights into etiology, diagnosis and treatment]. / Kongenitalni hiperinzulinizam- -novosti o nastanku, dijagnosticiranju i lijecenju bolesti.

Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia in the neonatal and early infancy periods. Althought the disease is relatively rare with incidence of about 1:25 000-50 000 live births, the importance of the disease should not be underestimated. Namely, prompt recognition and management of patients with CHI is essential, if permanent neurological impairment is to be avoided. CHI is caused by mutations in one of the 7 genes involved in the regulation of insulin secretion in pancreatic beta-cells. It is important to introduce specific medical therapy as soon as diagnosis is established. Severe, neonatal forms of CHI are often resistant to medications, thus they require surgical procedure. The preoperative genetic testing and scintigraphy are indicated to distinguish histological subtypes of the disease (focal vs. diffuse CHI). Patients with focal disease are usually cured after pancreatic resection, while diffuse disease has much worse prognosis. This manuscript offers novel insights into CHI and emphasizes the role of early diagnosis as crucial for succesful treatment that was recently enriched with novel options.

[Vitamin B12 deficiency in children--underestimated danger in the light of new knowledge]. / Manjak vitamina B12 u djece --podcijenjena opasnost u svjetlu novih spoznaja.

Vitamin B12 (cobalamin) has two active forms, adenosylcobalamin and methylcobalamin which have a key role in two important metabolic pathways in humans and their deficiency is responsible for clinical problems. Cobalamin is essential during whole life, but its sufficient amount is extra important in fetal and neonatal period, when it is essential for normal child growth and development as well as for normal development of the central nervous system. Because of very complex transport and metabolism, its deficiency can be manifested in numerous congenital and acquired disorders. Vitamin B12 deficiency mostly has non-specific clinical features, it carries a great risk of permanent consequences, but most frequently it is easily curable if diagnosed on time. In Croatia cobalamin deficiency in children has been diagnosed too rarely. Accordingly, the aim of this paper is to point to the recently gained knowledge on cobalamin metabolism, present typical case reports and to provide guidelines for rapid and proper diagnostic and therapeutic approach.

Expanding the known phenotype of Mullegama-Klein-Martinez syndrome in male patients.

Here, we report a novel case of a male patient with a hemizygous missense variant in STAG2 (p.Tyr159His) resulting in Mullegama-Klein-Martinez syndrome (MKMS), a rare X-linked cohesinopathy. He shares distinct clinical features with a previously reported male patient carrying the STAG2 variant p.Tyr159Cys, suggesting that this phenotype is determined by the position of the mutation. Additionally, our patient exhibits symptoms not previously associated with MKMS, expanding the known clinical phenotype of this rare disease.

Expanding the clinical spectrum of pathogenic variation in NR2F2: Asplenia.

We present a case with congenital syndromic asplenia associated with immune deficiency, glandular hypospadias and cryptorchidism. Genetic analysis identified a likely pathogenic de novo variant in NR2F2. Pathogenic NR2F2 variants have been associated with other congenital anomalies affecting the central axis, such as congenital heart disease and diaphragmatic hernia, which were not part of our patient's clinical features. The association between NR2F2 and asplenia (including glandular hypospadias and cryptorchidism) has been described in animal models and our report is the first expanding the NR2F2 clinical spectrum in humans to include asplenia.

Pallister Killian syndrome: unusual significant postnatal overgrowth in a girl with otherwise typical presentation.

Pallister Killian syndrome (PKS) is a rare genetic disorder caused by tetrasomy of the short arm of chromosome 12, revealed usually in mosaic distribution of an extra i (12) (p10) chromosome in fibroblasts. The syndrome presents with a recognizable pattern of findings including pigmentary skin changes, coarse face, high forehead, sparse anterior scalp hair, hypertelorism, seizures and progressive psychomotor developmental delay. It was first described independently by Pallister in 1977 and by Killian and Teschler-Nikola in 1981. We report a case of 21 month old girl with PKS and significant overgrowth. Cytogenetic analysis was performed using the GTG banding technique. The karyotype of cultured lymphocytes was normal. The karyotype from skin fibroblasts was established as mosaic tetrasomy of 12p 47,XX,+i (12) (p10)/46,XX. The origin of the extra marker chromosome was determinated by fluorescence in situ hybridization with chromosome 12 specific DNA probes confirming that supernumerary marker is chromosome i (12p) in 68% of cells. Despite the excessive postnatal growth we found low serum growth hormone levels and reduced response to pharmacological stimulation test. This is also the first report of a postnatal patient in our country.