Fakülteler / Faculties
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Item BCKDK Deficiency: A Treatable Neurodevelopmental Disease Amenable to Newborn Screening(2023) Ozturkmen Akay, Hatice; 36729635There are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum. Moreover, this is the first study to present newborn screening findings and mid-term clinical outcome. In this cross-sectional study, patients with a diagnosis of BCKDK deficiency were recruited via investigators' practices through a MetabERN initiative. Clinical, biochemical and genetic data were collected. Dried blood spot (DBS) newborn screening (NBS) amino acid profiles were retrieved from collaborating centres and compared to a healthy newborn reference population. Twenty-one patients with BCKDK mutations were included from 13 families. Patients were diagnosed between 8 months and 16 years (mean: 5.8 years, 43% female). At diagnosis, BCAA levels (leucine, valine and isoleucine) were below reference values in plasma and in CSF. All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18, 16/16 intellectual disability, 17/17 language impairment, 12/17 autism spectrum disorder, 9/21 epilepsy, 12/15 clumsiness, 3/21 had sensorineural hearing loss and 4/20 feeding difficulties. No microcephaly was observed at birth, but 17/20 developed microcephaly during follow-up. Regression was reported in six patients. Movement disorder was observed in 3/21 patients: hyperkinetic movements (1), truncal ataxia (1) and dystonia (2). After treatment with a high-protein diet (>= 2 g/kg/day) and BCAA supplementation (100-250 mg/kg/day), plasma BCAA increased significantly (P < 0.001), motor functions and head circumference stabilized/improved in 13/13 and in 11/15 patients, respectively. Among cases with follow-up data, none of the three patients starting treatment before 2 years of age developed autism at follow-up. The patient with the earliest age of treatment initiation (8 months) showed normal development at 3 years of age. NBS in DBS identified BCAA levels significantly lower than those of the normal population. This work highlights the potential benefits of dietetic treatment, in particular early introduction of BCAA. Therefore, it is of utmost importance to increase awareness about this treatable disease and consider it as a candidate for early detection by NBS programmes. Tangeraas et al. describe the largest series of BCKDK deficiency patients to date, including responses to dietetic treatment. Early introduction of BCAA ameliorates the BCKDK deficiency phenotype. This treatable neurodevelopmental disease should be considered for inclusion in newborn screening programmes.Item Is Celiac Disease an Etiological Factor in Children with Nonsyndromic Intellectual Disability?(2016) Sezer, Taner; Balci, Oya; Ozcay, Figen; Bayraktar, Nilufer; Alehan, Fusun; https://orcid.org/0000-0002-2278-1827; https://orcid.org/0000-0002-8402-8208; https://orcid.org/0000-0002-5214-516X; https://orcid.org/0000-0002-7886-3688; 26078418; AAJ-5931-2021; AAI-9346-2021; ABG-5684-2020; Y-8758-2018To determine the prevalence of celiac disease in children and adolescents with nonsyndromic intellectual disability, we investigated serum levels of tissue transglutaminase antibody and total IgA from 232 children with nonsyndromic intellectual disability and in a healthy control group of 239 children. Study participants who were positive for tissue transglutaminase antibody underwent a duodenal biopsy. A total of 3 patients in the nonsyndromic intellectual disability group (5.45%) and 1 in the control group (0.41%) had positive serum tissue transglutaminase antibody (P > .05). Duodenal biopsy confirmed celiac disease in only 1 patient who had nonsyndromic intellectual disability. In this present study, children with nonsyndromic intellectual disability did not exhibit a higher celiac disease prevalence rate compared with healthy controls. Therefore, we suggest that screening test for celiac disease should not be necessary as a part of the management of mild and moderate nonsyndromic intellectual disability. However, cases of severe nonsyndromic intellectual disability could be examined for celiac disease.Item Assessment of dental pain in children with intellectual disability using the dental discomfort questionnaire(2021) Senirkentli, Guler Burcu; Tirali, Resmiye Ebru; Bani, Mehmet; 33499707Objective: This study aimed to compare the Dental Discomfort Questionnaire (DDQ) scores in children with and without intellectual disability (ID) and to measure correlation between the total DDQ and the Decayed, Missing, and Filled Teeth (DMFT/dmft) scores, as well as the condition of the tooth causing pain. Method: This cross-sectional study included 81 children with normal intellectual development who attended the Departments of Pediatric Dentistry at two Turkish Universities and 80 children with different levels of intellectual disability who reported dental pain in special education centers. The 12-question DDQ (Turkish version) was applied to the parents of the patients with their consent. The relationship of the DDQ scores with tha of the DMFT/dmft, dental status, and demographic data was evaluated. Results: When the DDQ scores of children with intellectual disabilities were evaluated, it was found that the majority of the answers given to the questions were statistically similar (p < 0.05) to those of children with normal cognitive level. In the questions in which "pain when eating and brushing teeth" was evaluated, a higher score was obtained, which led to an increase in the total DDQ score (p < 0.001). There was a statistically significant difference between the groups in terms of the distribution of dental conditions (p < 0.001). When compared to the normal cognitive group, patients with mild and severe intellectual disabilities had more deep dentin caries, thoughy, frequent periapical abscess was less common in those groups (p < 0.001 and p = 0.022). There was no statistically significant relationship between DMFTscores. Conclusion: The DDQ was found to be a descriptive, functional, and easy-to-use questionnaire for children with intellectual disabilitiesin terms of detecting the presence of dental pain. No correlation was found between DMFT/dmft, dental status and DDQ scores.Item Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect(2019) Yalnizoglu, Dilek; Ozgul, R. Koksal; Oguz, Kader K.; Ozer, Bugra; Yucel-Yilmaz, Didem; Gurbuz, Berrak; Serdaroglu, Esra; Erol, Ilknur; Topcu, Meral; Dursun, Ali; 30701556MBOAT7 gene codes O-acyltransferase domain containing seven proteins which is one of four enzymes involved in remodeling of phosphoinositol phosphate (PIP) in LANDs cycle. We present clinical, neuroimaging, and genetic findings of 12 patients from 7 families with MBOAT7 gene defect, a recently defined novel phospholipid remodelling disease. To the best of our knowledge, our case series is the second report on patients with MBOAT7 gene defect. The patients present with global developmental delay particularly in speech and language skills, intellectual disability, stereotypical behavior, ataxic gait, early onset epilepsy with well response to medical treatment, strabismus and similar facial features. Common neuroimaging findings of the patients were folium dysgenesis of the cerebellum with a particular appearance, mild-to-moderate cerebellar atrophy, T2 hyperintensity of bilateral globus pallidius and dentate nuclei, enlarged perivascular areas, and mild thinning of the corpus callosum. Genome-wide genotyping and exome sequencing identified five different types of homozygous mutations in the MBOAT7 gene in all seven families which are p.Arg87*, p.Leu227ProfsX65, p.Gln376Lys, p.Trp426*, and chr19:54.666.173-54.677.766/11594bp del. We conclude that clinical and neuroimaging findings of MBOAT7 gene defect may suggest the diagnosis and guide genetic tests.