Vacuolated lymphocytes signifying a metabolic disorder in an infant with developmental delay.
Ontology highlight
ABSTRACT:
SUBMITTER: Salama R
PROVIDER: S-EPMC4706402 | biostudies-other | 2016 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Increasing evidence suggests that autism spectrum disorder (ASD) and many forms of developmental delay (DD) originate during fetal development. Preeclampsia may trigger aberrant neurodevelopment through placental, maternal, and fetal physiologic mechanisms.To determine whether preeclampsia is associated with ASD and/or DD.The Childhood Autism Risks from Genetics and the Environment (CHARGE) study is a population-based, case-control investigation of ASD and/or DD origins. Children from 20 California counties aged 24 to 60 months at the time of recruitment and living in catchment areas with a biological parent fluent in English or Spanish were enrolled from January 29, 2003, through April 7, 2011. Children with ASD (n?=?517) and DD (n?=?194) were recruited through the California Department of Developmental Services, the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, and referrals. Controls with typical development (TD) (n?=?350) were randomly selected from birth records and frequency matched on age, sex, and broad geographic region. Physicians diagnosing preeclampsia were masked to neurodevelopmental outcome, and those assessing neurodevelopmental function were masked to preeclampsia status.Preeclampsia and placental insufficiency were self-reported and abstracted from medical records.The Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised were used to confirm ASD, whereas children with DD and TD were confirmed by Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales and were free of autistic symptoms. Hypotheses were formulated before data collection.Children with ASD were twice as likely to have been exposed in utero to preeclampsia as controls with TD after adjustment for maternal educational level, parity, and prepregnancy obesity (adjusted odds ratio, 2.36; 95% CI, 1.18-4.68); risk increased with greater preeclampsia severity (test for trend, P?=?.02). Placental insufficiency appeared responsible for the increase in DD risk associated with severe preeclampsia (adjusted odds ratio, 5.49; 95% CI, 2.06-14.64).Preeclampsia, particularly severe disease, is associated with ASD and DD. Faulty placentation manifests in the mother as preeclampsia with vascular damage, enhanced systemic inflammation, and insulin resistance; in the placenta as oxygen and nutrient transfer restriction and oxidative stress; and in the fetus as growth restriction and progressive hypoxemia. All are potential mechanisms for neurodevelopmental compromise.
| S-EPMC4416484 | biostudies-literature
Project description:BACKGROUND:FOXG1 gene mutations have been associated with the congenital variant of Rett syndrome (RTT) since the initial description of two patients in 2008. The on-going accumulation of clinical data suggests that the FOXG1-variant of RTT forms a distinguishable phenotype, consisting mainly of postnatal microcephaly, seizures, hypotonia, developmental delay and corpus callosum agenesis. CASE PRESENTATION:We report a 6-month-old female infant, born at 38 weeks of gestation after in vitro fertilization, who presented with feeding difficulties, irritability and developmental delay from the first months of life. Microcephaly with bitemporal narrowing, dyspraxia, poor eye contact and strabismus were also noted. At 10 months, the proband exhibited focal seizures and required valproic acid treatment. Array-Comparative Genomic Hybridization revealed a 4.09 Mb deletion in 14q12 region, encompassing the FOXG1 and NOVA1 genes. The proband presented similar feature with patients with 14q12 deletions except for dysgenesis of corpus callosum. Disruption of the NOVA1 gene which promotes the motor neurons apoptosis has not yet been linked to any human phenotypes and it is uncertain if it affects our patient's phenotype. CONCLUSIONS:Since our patient is the first reported case with deletion of both genes (FOXG1-NOVA1), thorough clinical follow up would further delineate the Congenital Rett-Variant phenotypes.
| S-EPMC4970234 | biostudies-other
Project description:Due to the rarity of this disorder, paying attention to diagnostic clues is important. Low valine formula seems to be effective in improvement of patient's symptoms. Prevention of consanguineous marriage is the best way to prevent this disease.
| S-EPMC8299097 | biostudies-literature
Project description:BackgroundTOP2B encodes type II topoisomerase beta, which controls topological changes during DNA transcription. TOP2B is expressed in the developing nervous system and is involved in brain development and neural differentiation. Recently, a de novo missense TOP2B variant (c.187C>T) has been identified in an individual with neurodevelopmental disorder (NDD). However, the association between TOP2B variants and NDDs remains uncertain.MethodsTrio-based whole-exome sequencing was performed on a 7-year-old girl, presenting muscle hypotonia, stereotypic hand movements, epilepsy, global developmental delay, and autism spectrum disorder. Brain magnetic resonance images were normal. She was unable to walk independently and spoke no meaningful words.ResultsWe found a de novo variant in TOP2B (NM_001330700.1:c.187C>T, p.(His63Tyr)), which is identical to the previous case. The clinical features of the two individuals with the c.187C>T variant overlapped.ConclusionOur study supports the finding that TOP2B variants may cause NDDs.
| S-EPMC7057084 | biostudies-literature
Project description:The bromodomain adjacent to zinc finger 2B gene (BAZ2B) encodes a protein involved in chromatin remodeling. Loss of BAZ2B function has been postulated to cause neurodevelopmental disorders. To determine whether BAZ2B deficiency is likely to contribute to the pathogenesis of these disorders, we performed bioinformatics analyses that demonstrated a high level of functional convergence during fetal cortical development between BAZ2B and genes known to cause autism spectrum disorder (ASD) and neurodevelopmental disorder. We also found an excess of de novo BAZ2B loss-of-function variants in exome sequencing data from previously published cohorts of individuals with neurodevelopmental disorders. We subsequently identified seven additional individuals with heterozygous deletions, stop-gain, or de novo missense variants affecting BAZ2B. All of these individuals have developmental delay (DD), intellectual disability (ID), and/or ASD. Taken together, our findings suggest that haploinsufficiency of BAZ2B causes a neurodevelopmental disorder, whose cardinal features include DD, ID, and ASD.
| S-EPMC7262739 | biostudies-literature
Project description:UnlabelledMucopolysaccharidosis III is a rare genetic disease characterized by progressive cognitive decline and severe hyperactivity that does not respond to stimulants. Somatic features are relatively mild. Patients are often initially misdiagnosed as having idiopathic developmental delay, attention deficit/hyperactivity disorder and/or autism spectrum disorders, putting them at risk for unnecessary testing and treatments.ConclusionChildren with developmental or speech delay, especially those with a characteristic somatic feature or behavioural abnormalities, should be screened for MPS III.
| S-EPMC3654162 | biostudies-literature
Project description:In pleiotropic diseases, multiple organ systems are affected causing a variety of clinical manifestations. Here, we report a pleiotropic disorder with a unique constellation of neurological, endocrine, exocrine, and haematological findings that is caused by biallelic MADD variants. MADD, the mitogen-activated protein kinase (MAPK) activating death domain protein, regulates various cellular functions, such as vesicle trafficking, activity of the Rab3 and Rab27 small GTPases, tumour necrosis factor-α (TNF-α)-induced signalling and prevention of cell death. Through national collaboration and GeneMatcher, we collected 23 patients with 21 different pathogenic MADD variants identified by next-generation sequencing. We clinically evaluated the series of patients and categorized the phenotypes in two groups. Group 1 consists of 14 patients with severe developmental delay, endo- and exocrine dysfunction, impairment of the sensory and autonomic nervous system, and haematological anomalies. The clinical course during the first years of life can be potentially fatal. The nine patients in Group 2 have a predominant neurological phenotype comprising mild-to-severe developmental delay, hypotonia, speech impairment, and seizures. Analysis of mRNA revealed multiple aberrant MADD transcripts in two patient-derived fibroblast cell lines. Relative quantification of MADD mRNA and protein in fibroblasts of five affected individuals showed a drastic reduction or loss of MADD. We conducted functional tests to determine the impact of the variants on different pathways. Treatment of patient-derived fibroblasts with TNF-α resulted in reduced phosphorylation of the extracellular signal-regulated kinases 1 and 2, enhanced activation of the pro-apoptotic enzymes caspase-3 and -7 and increased apoptosis compared to control cells. We analysed internalization of epidermal growth factor in patient cells and identified a defect in endocytosis of epidermal growth factor. We conclude that MADD deficiency underlies multiple cellular defects that can be attributed to alterations of TNF-α-dependent signalling pathways and defects in vesicular trafficking. Our data highlight the multifaceted role of MADD as a signalling molecule in different organs and reveal its physiological role in regulating the function of the sensory and autonomic nervous system and endo- and exocrine glands.
| S-EPMC7447524 | biostudies-literature
Project description: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.
| S-EPMC8757376 | biostudies-literature
Project description:Hyperphenylalaninemia, movement disorder, and intellectual disability due to variants in DNAJC12 is a recently reported inherited neurotransmitter disorder. We report two new patients with this new genetic disorder. Patient 1 is a 6-year-11-month-old boy with mild hyperphenylalaninemia and global developmental delay (GDD). Seventeen-year-old male sibling of patient 1 had GDD from the first year of life. He had mild hyperphenylalaninemia at 11.5 years of age following his younger brother's diagnosis. He had low levels of homovanillic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid. Whole-exome sequencing (WES) was normal in 2016. After the first description of DNAJC12-associated hyperphenylalaninemia, dystonia, and intellectual disability in 2017, WES re-analysis identified a homozygous c.58_59delGG (p.(Gly20Metfs*2)) variant in DNAJC12. His younger brother was homozygous for the same variant, confirming the diagnosis of DNAJC12-associated hyperphenylalaninemia, movement disorder, and intellectual disability. Mild hyperphenylalaninemia and GDD should warrant targeted DNAJC12 genetic testing for the early diagnosis of DNAJC12-associated hyperphenylalaninemia, movement disorder, and intellectual disability.
| S-EPMC6244406 | biostudies-literature
Project description: Not available
| S-EPMC9493353 | biostudies-literature