A novel presentation of an ATP1A3 gene mutation - case report and literature review.

OBJECTIVE: Mutations in the ATP1A3 gene cause the classical disorders of rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC) and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). However, intermediate phenotypes have also been described, making the range of clinical manifestations associated with mutations in the ATP1A3 gene wider. A rare case of an ATP1A3 gene mutation is presented. CASE REPORT: Genetic testing was performed in a neonate who presented with neurological abnormalities on day 2 of life, severe electrolytic disturbances a few days later and developmental delay and epilepsy a few months later. A pathogenic heterozygous missense mutation in the ATP1A3 gene (c.2482G>A, E828K(p.Glu828Lys) was detected on clinical exome sequencing. CONCLUSIONS: The present case report extends the already described phenotypic variation observed in individuals with ATP1A3 gene mutations. It also illustrates the importance of genetic testing in the case of complex and not straightforward clinical scenarios, particularly when present from a very young age, before clinical criteria for known diagnoses are met.

Clinical and microbiological profile of persistent coagulase-negative staphylococcal bacteraemia in neonates.

An atypical pattern of coagulase-negative staphylococcal (CoNS) sepsis, characterized by persistence despite aggressive antibiotic therapy, has been described in neonates cared for in neonatal intensive-care units. Our aim was to analyse the clinical, microbiological and molecular determinants of this persistent CoNS bacteraemia. Neonates with late-onset CoNS bacteraemia were studied for a 2-year period. Demographic, clinical, laboratory, microbiological and molecular data were compared between neonates with persistent (≥3 consecutive positive blood cultures) and non-persistent CoNS bacteraemia. Twenty-nine infants with persistent and 43 with non-persistent bacteraemia were identified, with no significant differences regarding demographic and clinical characteristics between the two groups. Of a total of 170 CoNS isolates, 80 showed biofilm production (54 persistent and 26 non-persistent; p 0.013), whereas 127 were positive for the icaA and icaD genes (74 persistent and 53 non-persistent; p 0.598). Sixty ica-positive isolates did not produce slime, whereas 13 ica-negative isolates showed biofilm production. Endotracheal intubation and the presence of central vascular catheters were significant risk factors for persistent bacteraemia, but, in a logistic regression model, only biofilm production was significantly related to the persistent form of the disease (p 0.005). In this study, persistent CoNS sepsis in neonates requiring intensive care was not related to most of the known clinical risk factors, and it was associated with severe thrombocytopenia. Isolates associated with persistent bacteraemia were more likely to produce biofilm, independently of the presence of the ica operon.