[131-I-meta-iodo-benzyl-guanidine therapy in childhood neuroblastoma.] / Gyermekkori neuroblastoma kezelésében alkalmazott 131-I-meta-jodo-benzil-guanidin terápia.

Neuroblastoma, representing one-tenth of childhood malignancies, is a clinically and prognostically heterogeneous disease. Survival in cases with poor prognosis has recently been significantly improved by rapidly evolving multimodal therapy. Our 4-year-old patient presented with bitemporal swelling and the diagnostic workup confirmed stage IV neuroblastoma (bone marrow and multiple bone metastases). While the tumor responded well to the initial treatment, it relapsed during post-consolidation therapy. As part of the salvage therapy for this high-risk disease with poor prognosis, 131-I-meta-iodo-benzyl-guanidine treatment was performed for the first time in our country, in a case of pediatric neuroblastoma. Neuroendocrine tissue cells express a norepinephrine transporter capable of uptaking the catecholamine analog meta-iodo-benzyl-guanidine. This mechanism makes it an adequate molecule for the imaging (123-I-meta-iodo-benzyl-guanidine) and target therapy (131-I-meta-iodo-benzyl-guanidine) of neuroendocrine tumors, including neuroblastoma. Treatment with 131-I-meta-iodo-benzyl-guanidine requires specific personnel and infrastructural equipment, particularly in pediatric cases. Careful organization and cooperation between nuclear medicine specialists and collaborating clinicians (pediatric oncologists and adult internists if necessary) are essential. Meta-iodo-benzyl-guanidine therapy, already routinely used abroad, has been considered as part of salvage therapy for recurrent neuroblastoma until now, but ongoing clinical trials suggest that it may become part of the first-line treatment soon. As the indications broaden, it is necessary to make it available for more and more children in our country. Orv Hetil. 2023; 164(39): 1550-1555.

[Association of giant cell hepatitis and autoimmune hemolytic anemia in infancy]. / Óriássejtes hepatitis és autoimmun haemolyticus anaemia társulása kisdedkorban.

Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AIHA) is a rare disorder with unfavorable prognosis, affecting infants and young children. The mortality rate is high, complications of acute liver failure, sepsis, or liver transplantation can be responsible for fatal outcomes. An 18-month-old child who was diagnosed previously with autoimmune hemolytic anemia, developed acute hepatitis and acute liver failure concomitant to the relapse of the disease. GCH-AIHA is characterized by Coombs positive hemolytic anemia and progressive liver injury, histologically defined by widespread giant cell transformation. Liver biopsy was performed to establish the diagnosis, histological examination confirmed the presence of multinuclear, giant cell hepatocytes. Corticosteroid and azathioprine treatment were started. As a result of subsequent rituximab treatment and intravenous immunoglobulin therapy, acute liver failure and anemia gradually resolved. The exact background of the association of the two entities is still unknown, an autoimmune mechanism is suspected. Conventional immunosuppressive treatment with corticosteroid and azathioprine seems to be ineffective in most cases, therefore second- and third-line therapies are required. Since the introduction of the anti-CD20 rituximab therapy, the prognosis of GCH-AIHA has improved significantly. Orv Hetil. 2023; 164(36): 1432-1436.

Next-Generation Sequencing-Based Genomic Profiling of Children with Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) represents a major cause of childhood leukemic mortality, with only a limited number of studies investigating the molecular landscape of the disease. Here, we present an integrative analysis of cytogenetic and molecular profiles of 75 patients with pediatric AML from a multicentric, real-world patient cohort treated according to AML Berlin-Frankfurt-Münster protocols. Targeted next-generation sequencing of 54 genes revealed 17 genes that were recurrently mutated in >5% of patients. Considerable differences were observed in the mutational profiles compared with previous studies, as BCORL1, CUX1, KDM6A, PHF6, and STAG2 mutations were detected at a higher frequency than previously reported, whereas KIT, NRAS, and KRAS were less frequently mutated. Our study identified novel recurrent mutations at diagnosis in the BCORL1 gene in 9% of the patients. Tumor suppressor gene (PHF6, TP53, and WT1) mutations were found to be associated with induction failure and shorter event-free survival, suggesting important roles of these alterations in resistance to therapy and disease progression. Comparison of the mutational landscape at diagnosis and relapse revealed an enrichment of mutations in tumor suppressor genes (16.2% versus 44.4%) and transcription factors (35.1% versus 55.6%) at relapse. Our findings shed further light on the heterogeneity of pediatric AML and identify previously unappreciated alterations that may lead to improved molecular characterization and risk stratification of pediatric AML.

Effects of energy expenditure gene polymorphisms on obesity-related traits in obese children.

OBJECTIVE: To assess the frequencies of common polymorphisms of genes associated with energy expenditure among Hungarian obese children and investigate their influences on obesity-related traits and metabolic complications of common childhood obesity. RESEARCH METHODS AND PROCEDURES: In a total of 528 obese children (age 13.2±2.6 years) an oral glucose tolerance test and determination of fasting serum lipid levels were carried out, blood pressure and resting energy expenditure were measured and the children were genotyped for the following gene polymorphisms: Trp64Arg of ß3-adrenoreceptor (ADRB3), -3826 A/G of uncoupling protein (UCP)-1, exon 8 45 bp del/ins and -866 G/A of UCP-2, -55 C/T of UCP-3, and Pro12Ala of peroxisome-proliferator activated receptor gamma-2. RESULTS: Carriers of the ADRB3 Arg64 allele had a significantly higher relative body weight and relative body mass index compared with non-carriers. The UCP-2 exon 8 del/ins polymorphism was associated with higher degree of obesity, insulin resistance, dyslipideamia and lower adjusted metabolic rate. Children with UCP-3 -55 T/T genotype had a significantly lower adjusted metabolic rate than the C allele carriers. CONCLUSION: We found evidence for associations between common polymorphisms of the ADRB3, the UCP-2 and UCP-3 genes and basic metabolic rate as well as level and metabolic consequences of common obesity among Hungarian school-aged children.

Association of n-6 long-chain polyunsaturated fatty acids to -866 G/A genotypes of the human uncoupling protein 2 gene in obese children.

AIM: To investigate the association of plasma fatty acids with the -866 G/A polymorphism of uncoupling protein 2 (UCP2) in obese children. METHODS: Fatty acid composition of plasma phospholipids and sterol esters were investigated in 80 obese children. RESULTS: Values of dihomo-gamma-linolenic acid (C20:3n-6) were significantly lower in children with the -866 A/A (n = 12) than in those with the -866 G/A (n = 34) or -866 G/G (n = 34) genotype in plasma phospholipids (3.01 [0.42] vs. 3.56 [1.02] vs. 3.53 [0.84], % weight/weight, median [interquartile range], p < 0.05), and were significantly lower in children with the -866 A/A genotype than in the other two groups in plasma sterol esters (0.73 [0.22] vs. 0.92 [0.23] vs. 0.94 [0.25], p < 0.05). Phospholipid C20:3n-6 and arachidonic acid (C20:4n-6) values showed only in children with the -866 G/G and -866 G/A genotypes significant positive correlations with plasma insulin concentrations. CONCLUSIONS: Significantly lower values of C20:3n-6 can be detected in obese children with the homozygous (-866 A/A) mutation of UCP2 than in equally obese children with heterozygous mutation or the normal genotype. High glucose-stimulated insulin response is associated with high plasma C20:3n-6 and C20:4n-6 values only in obese children with the G allele of the -866 G/A polymorphism.

Effect of childhood obesity and obesity-related cardiovascular risk factors on glomerular and tubular protein excretion.

UNLABELLED: There is increasing evidence that obesity may damage the kidney in otherwise healthy individuals. Our study investigated the effect of childhood obesity on urinary albumin and beta-2-microglobulin excretion, and the association of these with obesity-related cardiovascular risk factors. Random morning spot urine samples were collected from clinically healthy obese (n = 86; median age 12.9 years, range 8.9-17.2 years; median weight 80.6 kg, range 46.1-136.8 kg; median body mass index 30.4 kg/m2, range 24.5-43.2 kg/m2) and normal weight children (n = 79; median age 13.5 years, range 10.7-14.9 years; median weight 51.0 kg, range 27.3-72.5 kg; median body mass index 18.2 kg/m2, range 13.2-23.9 kg/m2). The obese children were examined for the presence of common obesity-related cardiovascular risk factors including hyperinsulinaemia, impaired glucose tolerance (IGT), dyslipidaemia, hypercholesterolaemia, and hypertension. Obese children had a significantly higher urinary albumin/creatinine ratio (U-ACR) (median 11.7 mg/g, interquartile range 12.9 mg/g versus median 9.0 mg/g, interquartile range 5.1 mg/g; P = 0.003) and urinary beta-2-microglobulin/creatinine ratio (U-BMCR) (median 63.9 microg/g, interquartile range 34.7 microg/g versus median 34.6 microg/g, interquartile range 44.1 microg/g; P < 0.001) than normal weight children. Among the obese children, the U-ACR was associated with fasting hyperinsulinaemia, IGT, and hypercholesterolaemia (all P < 0.05), and significantly correlated with the fasting (r = 0.23, P < 0.05) and 2-h (r = 0.37, P < 0.001) plasma glucose levels measured during an oral glucose tolerance test. Obese children with no more than one of the features of the metabolic syndrome had significantly lower U-ACRs than obese children with two or more features (median 10.4 mg/g, interquartile range 5.8 mg/g versus median 15.3 mg/g, interquartile range 14.9 mg/g; P < 0.05). CONCLUSION: According to our results, clinically healthy obese children have a higher degree of albuminuria and beta-2-microglobulinuria than normal weight children, indicating early renal glomerular and tubular dysfunction as a consequence of childhood obesity. The urinary albumin/creatinine ratio in the obese children was associated with certain metabolic derangements linked to obesity, and also with the clustering of features of the metabolic syndrome.