Expansion of clinical and variant spectrum of EEF2-related neurodevelopmental disorder: Report of two additional cases.

Eukaryotic translation elongation factor 2 (eEF2), encoded by the gene EEF2, is an essential factor involved in the elongation phase of protein translation. A specific heterozygous missense variant (p.P596H) in EEF2 was originally identified in association with autosomal dominant adult-onset spinocerebellar ataxia-26 (SCA26). More recently, additional heterozygous missense variants in this gene have been described to cause a novel, childhood-onset neurodevelopmental disorder with benign external hydrocephalus. Herein, we report two unrelated individuals with a similar gene-disease correlation to support this latter observation. Patient 1 is a 7-year-old male with a previously reported, de novo missense variant (p.V28M) who has motor and speech delay, autism spectrum disorder, failure to thrive with relative macrocephaly, unilateral microphthalmia with coloboma and eczema. Patient 2 is a 4-year-old female with a novel de novo nonsense variant (p.Q145X) with motor and speech delay, hypotonia, macrocephaly with benign ventricular enlargement, and keratosis pilaris. These additional cases help to further expand the genotypic and phenotypic spectrum of this newly described EEF2-related neurodevelopmental syndrome.

Contribution of Mendelian Disorders in a Population-Based Pediatric Neurodegeneration Cohort.

OBJECTIVE: To evaluate Mendelian causes of neurodegenerative disorders in a cohort of pediatric patients. STUDY DESIGN: Patients enrolled in the Center for Applied Genomics Biobank at the Children's Hospital of Philadelphia with neurodegenerative symptoms were identified using an algorithm that consisted of including and excluding selected International Classification of Diseases, 9th and 10th edition codes. A manual chart review was then performed to abstract detailed clinical information. RESULTS: Of approximately 100 000 patients enrolled in the Center for Applied Genomics Biobank, 76 had a neurodegenerative phenotype. After chart review, 7 patients were excluded. Of the remaining 69 patients, 42 had a genetic diagnosis (60.9%) and 27 were undiagnosed (39.1%). There were 32 unique disorders. Common diagnoses included Rett syndrome, mitochondrial disorders, and neuronal ceroid lipofuscinoses. CONCLUSIONS: The disorders encountered in our cohort demonstrate the diverse diseases and pathophysiology that contribute to pediatric neurodegeneration. Establishing a diagnosis often informed clinical management, although curative treatment options are lacking. Many patients who underwent genetic evaluation remained undiagnosed, highlighting the importance of continued research efforts in this field.

Prevalence and Utility of Low Mean Corpuscular Volume in Infants Admitted to the Neonatal Intensive Care Unit.

OBJECTIVE: To determine the prevalence of low mean corpuscular volume (MCV) in newborn infants admitted to the neonatal intensive care unit and to assess low MCV as a diagnostic test for alpha thalassemia. STUDY DESIGN: Retrospective analysis of all infants admitted to the neonatal intensive care unit between January 2010 and October 2018 for which a complete blood count was performed during the first 3 postnatal days. Infants with a low MCV were compared with those with a normal MCV. Infants with positive hemoglobin Bart (Hb Bart) were compared with those withnegative Hb Bart. Low MCV was also evaluated as a diagnostic test for alpha thalassemia. RESULTS: A total of 3851 infants (1386 preterm, 2465 term) met the inclusion criteria and 853 (22.2%) had a low MCV. A low MCV was more common in term (25%) compared with preterm infants (17.1%, P < .001). Hb Bart positive newborn screening was identified in 133 infants (3.5%). Hb Bart was positive in 11.1% of infants with low MCV compared with 1.3% with normal MCV (P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of low MCV for the diagnosis of alpha thalassemia were 71.4%, 79.6%, 11.3%, and 98.7%, respectively. CONCLUSIONS: As Hb Bart positive newborn screens were seen in only 11.1% of infants with microcytosis, further diagnostic investigation may be warranted in individual infants. Further research to correlate microcytosis with iron status in infants and mothers is needed as well as studies using DNA analysis for the evaluation of alpha thalassemia variants.

Is an increased dwell time of a peripherally inserted catheter associated with an increased risk of bloodstream infection in infants?

OBJECTIVE: To estimate the risk of bloodstream infection associated with catheter dwell time in infants. DESIGN: Retrospective study. SETTING: Duke University Medical Center neonatal intensive care unit, an academic, level 3 nursery in Durham, North Carolina. METHODS: A case of catheter-associated bloodstream infection was defined as one that occurred in an infant whose culture-positive blood sample was collected more than 24 hours after catheter insertion or within 72 hours after catheter removal. We used multivariable logistic regression to control for the catheter's position and dwell time as well as the infant's sex, gestational age, age at time of catheter insertion, birth weight, and weight at time of catheter insertion. RESULTS: We identified 135 cases of catheter-associated bloodstream infection. The mean catheter dwell time was 12.2 days (range, 0-113 days), and the mean time to bloodstream infection was 10.8 days (range, 1-57 days). An increase in catheter dwell time was associated with a lower risk of bloodstream infection (odds ratio, 0.975 [95% confidence interval, 0.954-0.996]; P = .02). CONCLUSION: No increased risk of catheter-associated bloodstream infection was observed with increased catheter dwell time. This may have been due to the infant's improved nutrition, decreased need for other invasive devices, and maturing skin and immune system as catheter dwell time increased.