scholarly journals Urine Organic Acids as Metabolic Indicators for Global Developmental Delay/Intellectual Disability in Chinese Children

2021 ◽  
Vol 8 ◽  
Author(s):  
Baiyu Chen ◽  
Yalan Zhan ◽  
Miriam Kessi ◽  
Shimeng Chen ◽  
Juan Xiong ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Organic Acids ◽  
Developmental Delay ◽  
Fatty Acid Biosynthesis ◽  
Ketone Bodies ◽  
Principal Component ◽  
Future Research ◽  
Global Developmental Delay ◽  
Negative Results ◽  
Urine Organic Acids

Objective: The purpose of this study was to search for differential metabolites in urine organic acids, and to characterize metabolic features that can be used to identify metabolites for exploration of global developmental delay (GDD)/intellectual disability (ID) etiology and pathogenesis.Methods: We screened positive test results that could explain GDD/ID from 1,253 cases, and the major differential metabolites in 132 urine organic acids from the 1,230 cases with negative results (863 GDD cases, 367 ID cases), and 100 typically developing children (TD). Non-supervisory principal component analysis and orthogonal partial least squares discriminant analysis were used to develop models to distinguish GDD/ID from TD children, and to detect major differential metabolites.Results: We get 23 positive results that could identify the cause of GDD/ID from 1253 cases diagnosed with GDD/ID. Among 1,230 negative results, we get the differential metabolites of the GDD group and the ID group had the same trend compared with the TD group. Twenty four differential metabolites were obtained from the GDD group, and 25 from the ID group (VIP > 1.0, p < 0.01). These differential metabolites were mainly related to the following pathways: the synthesis and degradation of ketone bodies, citrate cycle, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, butanoate metabolism, pyruvate metabolism, fatty acid biosynthesis, valine, leucine and isoleucine degradation.Conclusion: The use of metabolomics research methods to detect urine organic acids of children with GDD/ID can discover differential metabolites, which might be valuable for future research on the etiology, pathogenesis, prognosis and possible interventions of GDD/ID. The significantly altered differential metabolites indicators could therefore be potential diagnostic biomarkers for GDD/ID.

scholarly journals Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay

2021 ◽  
Author(s):  
Uirá Souto Melo ◽  
Devon Bonner ◽  
Kevin C. Kent Lloyd ◽  
Ala Moshiri ◽  
Brandon Willis ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Global Developmental Delay ◽  
Loss Of Function

scholarly journals Characteristics of seizure frequency among Malaysian children diagnosed with structural– metabolic epilepsy

2012 ◽  
Vol 03 (03) ◽  
pp. 244-250 ◽  
Author(s):  
Muhannad RM Salih ◽  
Mohd Baidi Bahari ◽  
Mohamed Azmi Ahmad Hassali ◽  
Asrul Akmal Shafie ◽  
Omer Qutaiba B Al-lela ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Seizure Frequency ◽  
Substantial Reduction ◽  
Focal Seizure ◽  
Global Developmental Delay ◽  
Neurology Clinic ◽  
Collection Form ◽  
Metabolic Epilepsy

ABSTRACT Introduction: Seizure-free patients or substantial reduction in seizure frequency are the most important outcome measures in the management of epilepsy. The study aimed to evaluate the patterns of seizure frequency and its relationship with demographics, clinical characteristics, and outcomes. Materials and Methods: A retrospective cohort study was conducted at the Pediatric Neurology Clinic, Hospital Pulau Pinang. Over a period of 6 months, the required data were extracted from the medical records using a pre-designed data collection form. Results: Seizure frequency showed no significant association with patient’s demographics and clinical characteristic. However, significant reduction in seizure frequency from the baseline to the last follow-up visit was only seen in certain subgroups of patients including Malays, females, patients <4 years of age, patients with global developmental delay/intellectual disability, and patients with focal seizure. There was no significant association between seizure frequency and rate of adverse events. Polytherapy visits were associated with higher seizure frequency than monotherapy visits (27.97 ± 56.66, 10.94 ± 30.96 attack per month, respectively) (P < 0.001). There was a clear tendency to get antiepileptic drugs used at doses above the recommended range in polytherapy (8.4%) rather than in monotherapy (1.4%) visits (P < 0.001). A significant correlation was found between seizure frequency and number of visits per patient per year (r = 0.450, P < 0.001). Conclusion: Among children with structural–metabolic epilepsy, Malays, females, patients <4 years of age, patients with global developmental delay/intellectual disability and patients manifested with focal seizure are more responsive antiepileptic drug therapy than the other subgroups of patients.

scholarly journals EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay

2020 ◽  
Vol 98 (6) ◽  
pp. 555-561
Author(s):  
Muhammad Umair ◽  
Mariam Ballow ◽  
Abdulaziz Asiri ◽  
Yusra Alyafee ◽  
Abeer Tuwaijri ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Global Developmental Delay ◽  
Speech Delay ◽  
Mild Intellectual Disability ◽  
Homozygous Variant

scholarly journals Genetic testing in patients with global developmental delay/intellectual disabilities. A review

2015 ◽  
Vol 88 (3) ◽  
pp. 288-292 ◽  
Author(s):  
Diana Miclea ◽  
Loredana Peca ◽  
Zina Cuzmici ◽  
Ioan Victor Pop
Keyword(s):  
Intellectual Disability ◽  
Genetic Testing ◽  
Developmental Disabilities ◽  
Developmental Delay ◽  
Chromosomal Abnormalities ◽  
Fragile X ◽  
Genetic Disorders ◽  
Global Developmental Delay ◽  
European Guidelines ◽  
High Prevalence

Genetic factors are responsible for up to 40 % developmental disability cases, such as global developmental delay/ intellectual disability (GDD/DI). The American and more recently, the European guidelines on this group of diseases state that genetic testing is essential and should become a standardized diagnostic practice. The main arguments for the necessity of implementing such a practice are: (1) the high prevalence of developmental disabilities (3% of the population); (2) the high genetic contribution to this type of pathology; (3) insufficient referral for genetic consultation. In an attempt to address these issues, the purpose of this paper is to present the genetic etiology of global developmental delay / intellectual disability with emphasis on the need to implement a genetic testing protocol for the patients with GDD/DI, as indicated by the current guidelines. Chromosomal abnormalities and fragile X syndrome are the most frequent causes of developmental disabilities and the techniques employed to detect such genetic disorders should be used as first line investigations of GDD/DI. 

scholarly journals Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

2021 ◽  
Author(s):  
Marjolein J. A. Weerts ◽  
Kristina Lanko ◽  
Francisco J. Guzmán-Vega ◽  
Adam Jackson ◽  
Reshmi Ramakrishnan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Neurodevelopmental Disorder ◽  
Epileptic Activity ◽  
Language Delay ◽  
Global Developmental Delay ◽  
Sequence Variants ◽  
Loss Of Function ◽  
Phenotypic Spectrum

Abstract Purpose Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.

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