First case of desmosterolosis diagnosed by prenatal whole exome sequencing.

Desmosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis resulting in multiple congenital abnormalities and syndromic intellectual disability. It is caused by defects in DHCR24, the gene encoding 3-ß-hydroxysterol-24-reductase (24-dehydrocholesterol reductase), which acts in conversion of cholesterol precursor desmosterol, hence resulting in elevated plasma desmosterol levels. To date, desmosterolosis has been reported in 10 patients. Here we report an eleventh patient with desmosterolosis, and the first one to be diagnosed antenatally. Diagnosis was made on whole exome sequencing after amniocentesis due to complex antenatal abnormalities including cerebellar hypoplasia, microgyria, aortic stenosis, and renal tract abnormalities. Sterol quantitation was subsequently done postnatally, which supported the diagnosis. Although the nonspecific features make desmosterolosis difficult to suspect, we demonstrate that disorders of cholesterol synthesis can be considered as a differential diagnosis antenatally.

Home phototherapy for neonatal jaundice in the UK: a single-centre retrospective service evaluation and parental survey.

Background: In the UK setting, where neonatal jaundice treatment is required, it is largely carried out in hospitals. However, it is possible to safely administer home phototherapy (HPT). Objective: To report on our centre's experience of HPT and its potential benefits. Design: Retrospective observational study performed as a service evaluation. Patients: Infants ≥35 weeks corrected gestational age with a weight of 2 kg and serum bilirubin ≤50 µmol/L above treatment thresholds. Controls were a matched group of infants who received inpatient phototherapy (IPT). Setting: The catchment area of two neonatal intensive care units, one special care unit and a birth centre at four different hospitals that is covered by a single neonatal community outreach nursing team in Birmingham, UK. Intervention: HPT was started either in the community or as a continuation of IPT. Controls received IPT. Main outcome measures: The rate of bilirubin reduction, hospital readmission rates and parental satisfaction. Results: 100 infants received HPT while 50 received IPT. No infant showed a progressive rise of serum bilirubin level while receiving HPT. The rate of bilirubin reduction was similar in both HPT and IPT groups (2.4±1.9 and 2.5±1.6 µmol/L/hour, respectively, MD=-0.1, 95% CI -0.74 to 0.53, p=0.74). Readmission rate was 3% in the HPT group. 97% of parents stated that the overall experience was good and 98% would choose HPT if they had their time all over again. Conclusion: Our programme suggests that HPT for neonatal jaundice can be carried out in a select group of infants. It helps in providing holistic family-centred care and is viewed positively by families.

Cerebrospinal fluid protein and glucose levels in neonates with a systemic inflammatory response without meningitis.

BACKGROUND: It has been estimated that paediatric meningitis without elevated CSF white cell count (pleocytosis) accounts for 0.5-12% of all cases of bacterial meningitis. CSF protein and glucose measurements are therefore essential in management but may be neglected in clinical practice. In order to improve recognition of bacterial meningitis in neonates and to enable adequate management and audit, we investigated whether a systemic inflammatory response in the absence of meningitis is associated with elevated CSF protein and reduced CSF glucose levels. A further aim was to determine whether abnormal levels of these parameters were associated with increased incidence of neurological damage. METHODS: As part of an audit into management of abnormal CSF findings in neonates, we conducted a retrospective analysis of neonates without meningitis as evident from normal CSF white blood cell counts and negative CSF culture. We compared data from neonates with fever (temperature > 38.0 °C) and/or elevated C-reactive protein (CRP) levels (> 5 mg/l) (possible sepsis) with data from neonates without fever or CRP elevation. RESULTS: We analysed results from a total of 244 neonates. CSF protein levels were 0.89 g/l (SD 0.37) in neonates without fever or elevated CRP (n = 26) and not significantly different from neonates with possible sepsis (n = 218) with 0.92 g/l (SD 0.40). CSF glucose levels in infants with possible sepsis were 2.71 (SD 0.83) mmol/l and not significantly different from infants without sepsis with 2.55 mmol/l (SD 0.34). CONCLUSIONS: CSF protein and glucose levels are not affected by a systemic inflammatory response syndrome if there is no meningitis.