Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.

Aicardi-Goutières syndrome: unusual neuro-radiological manifestations.

Aicardi-Goutières syndrome (AGS) is one of the expanding group of inherited congenital infection like syndromes. Here, we describe the detailed clinical and imaging findings of two sibs with AGS. Each shows scattered periventricular intracranial calcifications, severe global delay, seizures, microcephaly and spasticity. Interestingly, chilblains were observed in the two sisters as well as their parents and a paternal uncle. The brain MRI of the older sister showed marked ventricular dilatation as a result of unusual associated porencephalic cysts. Unexpectedly, unilateral cerebellar hypoplasia was also noted. In comparison, her younger sister displayed the classic atrophic changes and white matter loss of AGS. The diagnosis of AGS was confirmed by sequence analysis, which identified a previously reported homozygous RNASEH2B mutation, c.554 T > G (p.V185G). Parents were heterozygous for the same mutation. Further molecular analysis excluded mutations in potentially related manifestations of COL4A1 gene. This is the first report of chilblains associated with heterozygous RNASEH2B mutation. Further, the brain imaging findings appear particularly interesting, which until now has not been reported in any AGS patient. We discuss the possible reasons for this unusual presentation.

Medical errors in neonatal intensive care unit at Benha University Hospital, Egypt.

This study was conducted in the neonatal intensive care unit of Benha University Hospital, Egypt from 1 August 2012 to the 31 January 2013 to identify medical errors and to determine the risk factors and consequences of these errors. Errors were detected by follow-up of neonates and review of reports including nursing followup sheets, resident progression notes and investigation reports. We detected 3819 errors that affected 97% of neonates. Types of errors included 403 medication errors (10.55% of total errors), 652 errors in daily routine procedures (17.07%), 1042 errors in invasive procedures (27.28%), 68 errors in nutrition (1.78%), 63 equipment errors (1.64%), 260 administration errors (6.8%), 656 staffing errors (17.18%), 107 environmental errors (2.8%), 448 infection control errors (11.73%) and 120 nosocomial infection errors (3.14%). Medical errors were high in low birth weight, low gestational age neonates and increased with duration of admission.

Assessment of serum zinc, selenium, and prolactin concentrations in critically ill children.

BACKGROUND: In critically ill patients, there are reduced stores of antioxidants, which are associated with increased organ failure and even higher mortality. Trace elements, especially zinc and selenium, are the cornerstone of the antioxidant defense in acute systemic inflammatory response syndrome. Prolactin (PRL) is the counterregulatory stress hormone that prevents cortisol/stress-induced lymphocyte apoptosis. The aim of our study is to detect the serum levels of zinc, selenium, and PRL hormone as important immunomodulators in critically ill children and to investigate the relationship between these immunomodulators and the severity of illness. SUBJECTS AND METHODS: This was a prospective study that included two groups; group 1: 50 critically ill children within 72 hours of intensive care unit admission, and group 2: 30 healthy children as controls. Blood samples were collected from the two groups for zinc, selenium, and PRL level measurement. RESULTS: Zinc and PRL levels were found to be decreased in critically ill children compared to control group, and these levels were inversely correlated with organ failure index and pediatric logistic organ dysfunction scores. Selenium levels were decreased in patients with sepsis and in patients with multiple organ failure. CONCLUSION: Serum concentrations of zinc and PRL are generally low in critically ill children, with a greater decrease in patients with sepsis and in the presence of multiple organ failure. The levels of zinc and PRL are inversely correlated with severity of illness. Selenium levels were decreased in patients with sepsis and in patients with multiple organ failure.