Çocuk Sağlığı ve Hastalıkları Anabilim Dalı Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12514/4204

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Citation - WoS: 1
Citation - Scopus: 2
Evaluation and management of neonatal onset hyperinsulinemic hypoglycemia: a single neonatal center experience
(Taylor & Francis, 2023) Bezirganoğlu, Handan; Okur, Nilifer; Feryal Taş, Funda; Çelik, Kıymet; Özbek, Mehmet Nuri
Objectives: To evaluate the clinical characteristics and treatment options of neonates requiring prolonged hospitalization due to persistent hyperinsulinemic hypoglycemia (HH). Methods: This retrospective cohort study included infants >34 weeks of gestation at birth who were born in our hospital between 2018 and 2021, diagnosed with HH, and required diazoxide within the first 28 days of life. The baseline clinical characteristics, age at the time of diagnosis and treatment options in diazoxide resistance cases were recorded. Genetic mutation analysis, if performed, was also included. Results: A total of 32 infants diagnosed with neonatal HH were followed up. Among the cohort, 25 infants were classified as having transient form of HH and seven infants were classified as having congenital hyperinsulinemic hypoglycemia (CHI). Thirty-one percent of the infants had no risk factors. The median birth weight was significantly higher in the CHI group, whereas no differences were found in other baseline characteristics. Patients diagnosed with CHI required higher glucose infusion rate, higher doses, and longer duration of diazoxide treatment than those in the transient HH group. Eight patients were resistant to diazoxide, and six of them required treatment with octreotide and finally sirolimus. Sirolimus prevented the need of pancreatectomy in five of six patients without causing major side effects. Homozygous mutations in the ABCC8 gene were found in four patients with CHI. Conclusions: The risk of persistent neonatal hyperinsulinism should be considered in hypoglycemic neonates particularly located in regions with high rates of consanguinity. Our study demonstrated sirolimus as an effective treatment option in avoiding pancreatectomy in severe cases.
Citation - WoS: 10
Citation - Scopus: 13
Glutaric aciduria and L-2-hydroxyglutaric aciduria: Clinical and molecular findings of 35 patients from Turkey
(ScienceDirect, 2023) Özbek, Mehmet Nuri; Ergül Bozaci, Ayse; Er, Esra; Ünal, Aysel Tekmenuray; Tas, Ibrahim; Ayaz, Ercan; Durmaz, Asude; Aykut , Ayçe; Kose, Melis
Background: Cerebral organic acid disorders are progressive neurometabolic diseases characterized by neurologic dysfunction. Glutaric aciduria type I (GA-I) and L-2-hydroxyglutaric aciduria (L2HGA) are the main cerebral organic acid disorders. They are both classified as, and it is suggested that these two disorders may share a common metabolic pathway. Current treatment strategies are based on levocarnitine, vitamin B2, and diet. Recent guidelines recommend a lysine-restricted diet up to six years of age, but there is no consensus for patients over the age of six. Vitamin B2 is exists in the blood as riboflavin and its cofactors, flavin mononucleotide and flavin adenine dinucleotide (FAD). FAD, the cofactor of L2HGD, accelerates the conversion of L-2-hydoxy glutarate to alpha-ketoglutarate. Levocarnitine stimulates the formation and excretion of derivatives of glutaric acid. Also, lysine-associated organic acidurias some results provide principal proof for the beneficial effects of riboflavin in GA-I. It has been previously reported that combination therapy with riboflavin and levocarnitine is effective for L2HGA as well as GA-I. Riboflavin and levocarnitine have been reported to improve not only clinical symptoms but also urinary 2-HGA levels. In our study, we aimed to evaluate the effect of the current treatment strategies and genotype on urinary metabolites and IQ scores in GA-I and L2HGA patients. Methods: The presented retrospective multicenter study included patients followed up in Diyarbakir Children's Hospital and Izmir Katip Celebi University Faculty of Medicine, Division of Pediatric Metabolism. Between 2016 and 2021, we retrospectively evaluated 35 patients with confirmed diagnosis of GA-I and L-2HGA. We analyzed the clinical, biochemical, neuroradiological, molecular data and treatment of the patients. The follow-up period was every 2 months until 12 months old, every 3 months until 6 years of age, and every 6 months thereafter. Therapy monitoring was undertaken during follow-up visits that included evaluation of clinical parameters, laboratory parameters, and dietary consumption records. Denver II was applied in order to evaluate children aged 0–6 years in terms of development. Patients between 6 and 16 years of age were evaluated using the Wechsler Intelligence Scale for Children-Revised. Results: We identified 25 with GA-I and 10 with L2HGA. The most common clinical symptoms were developmental delay, intellectual disability, and movement disorders. Behavioural problems were more common in L2HGA than in GA-I patients. In the same family, there were patients with severe developmental delay despite early diagnosis and treatment and individuals with normal IQ scores. In our study group, we used diet (lysine restricted or protein controlled), levocarnitine and vitamin B2 for GA-I patients. The mean urinary glutaric acid levels were decreased with treatment in GA-I patients. Group I consisted of 14/25 patients receiving lysine restricted diet and levocarnitine, Group II (8/25) received protein-controlled diet and levocarnitine. Group III (3/25) patients whom had p.Pro248Leu (P248L) variant, received riboflavin in combination with protein-controlled diet and levocarnitine. When we evaluated according to the treatment groups, a significant decrease was observed in urinary glutaric acid levels in group I. But there were no significant difference in Group II and III. The patients with c.1018C > T variant in GCDH gene had higher pre-treatment urinary metabolites and significant reduction in urinary metabolites with treatment was detected. In L2HGA patients, we used levocarnitine and vitamin B2. In all L2HGA patients, there was a significant decrease in the mean urinary 2- hydoxy glutarate with treatment. However, there was no significant difference between the c.164G > A and c.1115delT variants. The mean pre- and post-treatment IQ scores of GA-I patients, no significant difference was observed. Relative neurologic improvement was seen in three L2HGA patients. We found two novel variants, including the c.221A > G (p.Tyr74Cys) in the GCDH gene and the c.738 + 5A > G splice variant in the L2HGDH gene. Conclusions: Glutaric aciduria type I and L2HGA are the most common cerebral organic acidurias. Early and correct diagnosis is crucial. Poor prognosis based on metabolic crises and progressive deterioration still appears. In countries where newborn screening is not performed, a clinical suspicion index is required for cerebral organic aciduria. GA-I and L-2HGA are difficult to examine by medical evidence standards because of the small sample size, regional differences in newborn screening, and medical care limits. More clinical studies are needed to identify effective treatments. However, the significant decrease in urinary glutaric acid levels after treatment in patients on lysine-restricted diet raises the question of whether lysine-restricted diet should be continued after six years of age. We also reported our experience in order to contribute to the literature.
Citation - WoS: 2
Citation - Scopus: 2
Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study
(Neuropediatrics, 2023) Özgün, Nezir; Günay , Çağatay; Aykol, Duygu; Özsoy, Özlem; Sönmezler, Ece; Hiz Kurul, Semra
Background: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. Methods: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Results: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. Conclusion: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

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