Methylmalonic aciduria and homocystinuria, cblC type, is a rare disorder of intracellular vitamin B(12) (cobalamin [Cbl]) metabolism caused by mutations in the MMACHC gene. MMACHC was sequenced from the gDNA of 118 cblC individuals. Eleven novel mutations were identified, as well as 23 mutations that were observed previously. Six sequence variants capture haplotype diversity in individuals across the MMACHC interval. Genotype-phenotype correlations of common mutations were apparent; individuals with c.394C>T tend to present with late-onset disease whereas patients with c.331C>T and c.271dupA tend to present in infancy. Other missense variants were also associated with late- or early-onset disease. Allelic expression analysis was carried out on human cblC fibroblasts compound heterozygous for different combinations of mutations including c.271dupA, c.331C>T, c.394C>T, and c.482G>A. The early-onset c.271dupA mutation was consistently underexpressed when compared to control alleles and the late-onset c.394C>T and c.482G>A mutations. The early-onset c.331C>T mutation was also underexpressed when compared to control alleles and the c.394C>T mutation. Levels of MMACHC mRNA transcript in cell lines homozygous for c.271dupA, c.331C>T, and c.394C>T were assessed using quantitative real-time RT-PCR. Cell lines homozygous for the late onset c.394C>T mutation had significantly higher levels of transcript when compared to cell lines homozygous for the early-onset mutations. Differential or preferential MMACHC transcript levels may provide a clue as to why individuals carrying c.394C>T generally present later in life.

The presence of an implanted pacemaker is widely regarded as an absolute contraindication to magnetic resonance (MR) imaging; however, this viewpoint is based largely on safety concerns in the 1982-1996 period. Since 1996, changes in pacemaker electronics including decreased ferromagnetic content, increased sophistication of the circuitry, and onboard computer capabilities suggest that the absolute contraindication of MR imaging for pacemaker patients should be reconsidered. In addition, there are now data from prospective trials of 232 patients with demand pacemakers who underwent MR imaging at 0.5-1.5 T. Although a variety of pacemaker parameters were evaluated before, during, immediately after, and 3 months after MR imaging, no significant pacemaker changes were identified. No patients reported abnormal sensations such as pacemaker movement or irregular heartbeats even at direct questioning. These results suggest that peripheral locations such as the brain and knee may be considered for MR imaging. Thus, pacemaker patients should be assessed individually for their suitability for MR imaging, which may be performed safely under defined conditions.

A joint statement with the College of Family Physicians of CanadaAll Canadian Paediatric Society position statements and practice points are reviewed regularly and revised as needed. Consult the Position Statements section of the CPS website www.cps.ca/en/documents for the most current version. Retired statements are removed from the website. AbstractNewborns are at risk for vitamin K deficiency bleeding (VKDB) caused by inadequate prenatal storage and deficiency of vitamin K in breast milk. Systematic review of evidence to date suggests that a single intramuscular (IM) injection of vitamin K at birth effectively prevents VKDB. Current scientific data suggest that single or repeated doses of oral (PO) vitamin K are less effective than IM vitamin K in preventing VKDB. The Canadian Paediatric Society and the College of Family Physicians of Canada recommend routine IM administration of a single dose vitamin K at 0.5 mg to 1.0 mg to all newborns. Administering PO vitamin K (2.0 mg at birth, repeated at 2 to 4 and 6 to 8 weeks of age), should be confined to newborns whose parents decline IM vitamin K. Health care providers should clarify with parents that newborns are at increased risk of VKDB if such a regimen is chosen. Current evidence is insufficient to recommend routine intravenous vitamin K administration to preterm infants undergoing intensive care.

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