The implementation of revised guidelines and the performance of a screening programme for congenital hypothyroidism.

OBJECTIVES: To see whether revised screening standards and health-professional training are associated with changes in the performance of a neonatal screening programme for congenital hypothyroidism (CHT). METHODS: Screening data from the regional screening service in Durham and Newcastle, which covers north-east England and North Cumbria. SETTING: We assessed the timing of the different stages of the screening process leading up to the introduction of the revised guidelines between April 2004 and March 2005 (year 1) and afterwards between April 2005 and March 2006 (year 2) in all babies notified as having CHT. We also assessed the interval between sampling and specimen arrival in the laboratory at the beginning and end of year 2 in all babies screened. RESULTS: Twenty-three babies tested positive or borderline in year 1 and 18 babies in year 2. There was reduced variability in the overall time from birth to notification in year 2 versus year 1 (P = 0.001). This reduction was a consequence of a reduced interval between sample collection and arrival in the laboratory (P = 0.047) and for the laboratory to notify the positive test result (P = 0.003). There was a reduction in the mean time from sampling to receipt by the laboratory in the 2997 babies screened in the final month compared with the 2498 babies screened in the first month of year 2 (P = 0.01). CONCLUSION: There was an improvement in neonatal screening programme performance around the time that revised neonatal screening guidelines were introduced. This highlights the importance of ongoing education and training for those involved in screening programmes.

Repeat testing for congenital hypothyroidism in preterm infants is unnecessary with an appropriate thyroid stimulating hormone threshold.

BACKGROUND: Revised UK neonatal screening guidelines recommend that a second blood sample for assay of thyroid stimulating hormone (TSH) be taken when preterm infants reach a postmenstrual age of 36 weeks. OBJECTIVE: To examine the results of a regional screening programme to see whether a rise in TSH concentration was observed in some preterm infants between the first sample taken around 5 days after delivery and the second sample taken at around 36 weeks. METHODS: Whole-blood TSH concentrations in preterm infants born over a 2-year period (April 2005 to March 2007) were assessed, and the number of infants in whom there was a fall or rise to values below or above the local screening threshold (6 mU/l) was determined. RESULTS: Baseline TSH samples were obtained from 2238 preterm infants (median gestational age 32 weeks, range 21-35) with second samples obtained from 2039 (median gestational 32 weeks, range 23-35). In 19 infants, TSH concentrations fell from above to below the screening threshold, and in five infants values rose from below the screening threshold to 6-10 mU/l. However, TSH concentrations fell to <6 mU/l on a further blood spot in four of these infants, and the remaining infant had a serum TSH of 6.8 mU/l. Three infants had raised TSH concentrations on both occasions with unequivocal hypothyroidism (serum TSH >80 mU/l). The initial TSH concentration in one of these infants was 6-10 mU/l. CONCLUSIONS: No infant with a normal TSH concentration on first sampling had a TSH concentration that rose above 10 mU/l on second sampling, and no infants with a normal TSH concentration on first screening are receiving long-term thyroxine treatment. This study suggests that a second sample may not be necessary with a screening threshold of 6 mU/l.

Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature.

BACKGROUND: Wolcott-Rallison syndrome is a rare autosomal recessive condition characterized by early infancy onset diabetes mellitus and multiple epiphyseal dysplasia. So far, 17 children have been described in the world literature. Recently, mutations in the gene encoding EIF2AK3 have been shown to segregate with the syndrome in three affected families. AIMS: We aimed to describe the clinical characterization and mutation analysis of a further child, and full clinical and follow-up details on our first family including the longest surviving child. METHODS: Retrospective case notes review of three children presenting to the diabetic unit at our institution; mutation analysis of the EIF2AK3 gene in our most recent patient; and review of the literature on Wolcott-Rallison syndrome. RESULTS: Previously unreported phenotypic features in our patients included developmental regression after episodes of hepatic failure, and pachygyria on brain imaging. We have identified a novel 4-base pair deletion (nt 3021-3024 del GAGA) in exon 13, which results in a frameshift and premature stop codon (R908 F/S +22X), causing premature truncation of the protein and abolition of the carboxy-segment of the catalytic domain. CONCLUSIONS: Wolcott-Rallison syndrome causes early-onset diabetes and acute hepatic failure, before epiphyseal dysplasia is manifest. We have identified a novel mutation in EIF2AK3, and prenatal diagnosis may now be offered to affected families.