[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.

Pancreatic family history does not predict disease progression but connotes alcohol consumption in adolescents and young adults with acute pancreatitis: Analysis of an international cohort of 2,335 patients.

Background: In pediatric acute pancreatitis (AP), a family history of pancreatic diseases is prognostic for earlier onset of recurrent AP (ARP) and chronic pancreatitis (CP). No evidence supports the same association in adult-onset pancreatitis. Age-specific reasons for familial aggregation are also unclear. We aimed to examine the prognostic role of pancreatic family history for ARP/CP and observe possible underlying mechanisms. Methods: We conducted a secondary analysis of the Hungarian Pancreatic Study Group's (HPSG) multicenter, international, prospective registry of patients with AP, both children and adults. We compared the positive family history and the negative family history of pancreatic diseases, in different age groups, and analyzed trends of accompanying factors. Chi-square and Fisher exact tests were used. Results: We found a higher rate of ARP/CP in the positive pancreatic family history group (33.7 vs. 25.9%, p = 0.018), peaking at 6-17 years. Idiopathic AP peaked in childhood in the positive family history group (75% 0-5 years) and was consistently 20-35% in the negative group. A higher rate of alcohol consumption/smoking was found in the positive groups at 12-17 years (62.5 vs. 15.8%, p = 0.013) and 18-29 years (90.9 vs. 58.1%, p = 0.049). The prevalence of diabetes and hyperlipidemia steadily rose with age in both groups. Conclusion: Positive family history most likely signifies genetic background in early childhood. During adolescence and early adulthood, alcohol consumption and smoking emerge-clinicians should be aware and turn to intervention in such cases. Contrary to current viewpoints, positive pancreatic family history is not a prognostic factor for ARP and CP in adults, so it should not be regarded that way.

Effect of joint transition visits on quality of life in adolescents with inflammatory bowel diseases: a protocol for a prospective, randomised, multicentre, controlled trial (TRANS-IBD).

INTRODUCTION: Inflammatory bowel diseases (IBD) are among the most common chronic illnesses diagnosed in childhood. Transition from paediatric to adult care is a crucial phase. The implementation of joint visits during the transition period in IBD is widely recommended, however, strong evidence supporting their benefit is still missing. In this trial, we aim to prove the superiority of joint visits compared with usual care in improving transition outcomes of adolescents with IBD. METHODS AND ANALYSIS: This is a randomised controlled two-arm multicentre trial. A minimum of 160 adolescents with IBD aged between 16.75 and 17 years will be recruited from Hungarian tertiary IBD centres. After randomisation, eligible subjects in the intervention arm attend a total of four joint visits with adult and paediatric gastroenterologist between the ages of 17 and 18. In the control arm, adolescents meet only the paediatric gastroenterologist, but there is a balanced consultation between the two gastroenterologist regarding the patient's treatment plan. Patients in both groups receive the same training and education, the only determinative difference between the two arms is the presence of the adult gastroenterologist at the joint visits. Data will be collected at inclusion, at transfer and 12 months post-transfer. Primary outcome is the change in health-related quality of life measured with the IMPACT-III questionnaire at 1 year after transfer. Secondary outcomes include the number of patients not lost to follow-up, healthcare utilisation, disease activity, medication adherence, self-efficacy, transition readiness and patient's satisfaction. To compare the results of the two patient groups, two-sample T-test and Mann-Whitney test will be applied. ETHICS AND DISSEMINATION: The Scientific and Research Ethics Committee of the Hungarian Medical Research Council approved this study (50457-2/2019/EKU). Findings will be disseminated at conferences and in medical journals. TRIAL REGISTRATION NUMBER: NCT04290156.

[Clinical classification of congenital limb abnormalities]. / Veleszületett végtagfejlodési rendellenességek klinikai osztályozása.

Limb developmental defects are well-known, conspicuous abnormalities. Until this day, the background has still not been completely revealed, however, the development of scientific methods provides more and more opportunities which may help to understand developmental processes and defects of this compound system. Considering these aspects, following data collection from patients with limb developmental defects, we began a study with the purpose of finding/establishing a classification system that is suitable for morphological and clinical distinctions, besides considering developmental aspects, and may help to indicate adequate genetic examinations. To classify 195 patients included in our database, we chose a worldwide accepted table from Swanson. Based upon our observations we proposed some alterations, which finally lead to a table, suitable for patient classification based upon morphology and clinical features. Furthermore it allows comparisons concerning developmental aspects, gives reasonable background for genetic studies and is suitable for everyday clinical usage.

Lithium suppresses epidermal SERCA2 and PMR1 levels in the rat.

Autosomal dominant mutations in the genes encoding the calcium ATPases SERCA2 and PMRI/SPCA1 cause the genodermatoses Darier disease (DD) and Hailey-Hailey disease (HHD), respectively. Recent observations indicated that the level of the pathogenic proteins greatly decreases in the affected areas of the epidermis in these disorders. Here we addressed how lithium, a recognized exacerbating factor in Darier disease, affects the epidermal expression of SERCA2 and PMR1/SPCA1 in the rat as a model. Standard histologic and immunohistochemical methods were utilized in 3 lithium-treated and 3 control animals. A significant suppression of epidermal SERCA2 and PMR1 levels were observed as a result of lithium therapy in addition to marked qualitative and quantitative changes in the stratum corneum and the granular layer of the epidermis in the treated animals. Our findings suggest that exacerbating factors in calcium ATPase disorders of the skin suppress epidermal SERCA2 and PMR1 levels, further decreasing the already haploinsufficient protein expression to a potentially critical level in Darier disease and Hailey-Hailey disease, respectively. Lithium therapy should specifically be avoided not only in Darier disease, but Hailey-Hailey disease as well.

[Novel approaches to the background of developmental abnormalities: clinical genetics of transcription factors]. / Uj lehetoségek a fejlodési rendellenességek hátterének feltárására: transzkripciós faktorok klinikai genetikája.

Transcription factors are highly conserved proteins with preserved structure and function for up to a hundred million years. They regulate protein formation and function by binding to DNA and controlling gene expression. Mutations are generally lethal, but can play role in endocrine disorders and tumor genesis. They are necessary for cell growth, proliferation, differentiation and are required in tissue and organ development during normal embryogenesis. Consequently, transcription factors are essential in developmental processes and homeostasis. Mutations of genes encoding transcriptional regulators have been shown to be involved in a number of various genetic diseases, in particular malformation of the skeletal system, cranium, limbs, as well as some congenital syndromes with anomalies of these organs and somatic/mental retardation. Evidences accumulate to support the need of transcription factor mutation identification in the clinical practice. The present study reviews the most important congenital malformations and genetic syndromes which are thought to be related to mutations in classic transcription factors, and in which determination of transcription factors might be of clinical significance, even in the near future, for exact causative diagnosis and genetic counseling in affected families. In addition, studies of the transcription factors may lead to a better understanding of human embryogenesis.

Females with PDHA1 gene mutations: a diagnostic challenge.

Biochemical analysis was performed in muscle tissue and in fibroblasts of four unrelated females consecutively diagnosed with a 'de novo' point mutation in the PDHA1 gene. Pyruvate dehydrogenase E1 subunit deficiency was confirmed in the muscle sample of all patients, however, in three out of four cases the activity of the pyruvate dehydrogenase complex in fibroblasts showed a normal activity. A skewed inactivation was confirmed of the maternal X chromosome in fibroblasts in all children. Due to the possibility of a skewed X inactivation pattern enzyme measurements in fibroblasts are not always reliable for the diagnosis of a PDHc defect in females. Based on the overlapping features of PDHc deficiency with those of the disorders of the oxidative phosphorylation we suggest performing a fresh muscle biopsy for detailed biochemical analysis in females with a suspected pyruvate dehydrogenase deficiency, followed by molecular genetic analysis of the PDHA1 gene.