scholarly journals Recessive mutations inSLC13A5result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia

Brain ◽  
2015 ◽  
Vol 138 (11) ◽  
pp. 3238-3250 ◽  
Author(s):  
Katia Hardies ◽  
Carolien G. F. de Kovel ◽  
Sarah Weckhuysen ◽  
Bob Asselbergh ◽  
Thomas Geuens ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Citrate Transport ◽  
Recessive Mutations

scholarly journals B.02 Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy

2018 ◽  
Vol 45 (s2) ◽  
pp. S12-S12
Author(s):  
HJ McMillan ◽  
A Telegrafi ◽  
A Singleton ◽  
M Cho ◽  
D Lelli ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Movement Disorders ◽  
Optic Atrophy ◽  
Early Recognition ◽  
Gene Mutations ◽  
Cortical Atrophy ◽  
Recessive Mutations ◽  
Severe Hypotonia ◽  
Funduscopic Examination ◽  
Facial Dyskinesia

Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.

scholarly journals NGLY1: Insights from C. elegans

2021 ◽  
Author(s):  
Nicolas John Lehrbach
Keyword(s):  
Transcription Factor ◽  
Motor Control ◽  
Developmental Delay ◽  
Genetic Model ◽  
C Elegans ◽  
Recessive Mutations ◽  
Dependent Sequence ◽  
Model Animal ◽  
Evolutionarily Conserved

Summary Peptide:N-glycanase is an evolutionarily conserved deglycosylating enzyme that catalyzes the removal of N-linked glycans from cytosolic glycoproteins. Recessive mutations that inactivate this enzyme cause NGLY1 deficiency, a multisystemic disorder with symptoms including developmental delay and defects in cognition and motor control. Developing treatments for NGLY1 deficiency will require an understanding of how failure to deglycosylate NGLY1 substrates perturbs cellular and organismal function. In this review, I highlight insights into peptide:N-glycanase biology gained by studies in the highly tractable genetic model animal C. elegans. I focus on the recent discovery of SKN-1A/Nrf1, an N-glycosylated transcription factor, as a peptide:N-glycanase substrate critical for regulation of the proteasome. I describe the elaborate post-translational mechanism that culminates in activation of SKN-1A/Nrf1 via NGLY1-dependent ‘sequence editing’ and discuss the implications of these findings for our understanding of NGLY1 deficiency.

Using parental questionnaires to identify developmental delay

2005 ◽  
Vol 47 (09) ◽  
pp. 646 ◽  
Author(s):  
Alan Emond ◽  
J Clare Bell ◽  
Jon Heron
Keyword(s):  
Developmental Delay

ACOX1-Deficiency Causing a Severe Developmental Delay and Epilepsy

2019 ◽  
Author(s):  
Simona Schröder ◽  
Hans Rudolf Waterham ◽  
M. S. Ebberink ◽  
Sacha Ferdinandusse ◽  
Juliane Spiegler
Keyword(s):  
Developmental Delay

Hearing and Neurodevelopmental Outcomes of Young Infants with Parechovirus-A and Enterovirus Meningitis: Cohort Study in Singapore Children and Literature Review

2020 ◽  
Author(s):  
Elis Yuexian Lee ◽  
Jessica Hui Yin Tan ◽  
Chew Thye Choong ◽  
Nancy Wen Sim Tee ◽  
Chia Yin Chong ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Oropharyngeal Dysphagia ◽  
Significant Risk ◽  
Developmental Outcomes ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Cortical Blindness ◽  
Speech Delay ◽  
Neurodevelopmental Outcomes ◽  
Young Infants

Abstract Parechovirus-A (PeV-A) and Enterovirus (EV) commonly cause childhood aseptic meningitis. Bacterial meningitis in children has been associated with devastating long-term sequelae. However, developmental outcomes are unclear in Parechovirus meningitis. This study aims to review the clinical findings and developmental outcomes of infants with PeV-A and EV meningitis. We performed a retrospective study of infants aged 90 days or younger being admitted to our hospital with PeV-A meningitis between November 2015 and July 2017, with positive cerebrospinal fluid (CSF) PeV-A PCR and negative blood and CSF bacterial cultures. Hearing and neurodevelopmental outcomes were compared with a previous cohort of infants aged 90 days or younger with EV meningitis admitted from January 2015 to December 2015. A total of 161 infants were included in our study, of which 68 infants (42.2%) had PeV-A meningitis and 93 infants (57.8%) had EV meningitis. We assessed their developmental outcome at 6 months, 1 year, and 2 years post-meningitis. At 2 years post-meningitis, three infants with PeV-A meningitis had developmental delay (5.5%), whereas none with EV meningitis had developmental delay. One patient had speech delay and autism spectrum disorder, while two had mild speech delay. When compared with our cohort of EV meningitis ≤90 days old, children with PeV-A meningitis ≤90 days old were more likely to have developmental delay 2 years post-meningitis (odds ratio 2.4, 95% confidence interval 2.0–3.0, p = 0.043). None of the patients with PeV-A or EV meningitis had sensorineural hearing loss or neurological sequelae, such as cortical blindness, oropharyngeal dysphagia, hydrocephalus, epilepsy, or cerebral palsy. Infants with PeV-A meningitis had a significant risk of developmental delay 2 years post-meningitis compared with those with EV meningitis. It is important to follow-up the developmental milestones of infants diagnosed with PeV-A meningitis for at least 2 years; and when they develop developmental delay, to ensure that they receive appropriate intervention.

Sign in / Sign up

Export Citation Format

Share Document