Mutational analysis of the IDUA gene was performed in a cohort of 102 European patients with mucopolysaccharidosis type I. A total of 54 distinct mutant IDUA alleles were identified, 34 of which were novel including 12 missense mutations, 2 nonsense mutations, 12 splicing mutations, 5 micro-deletions, 1 micro-duplication 1 translational initiation site mutation, and 1 'no-stop' change (p.X654RextX62). Evidence for the pathological significance of all novel mutations identified was sought by means of a range of methodological approaches, including the assessment of evolutionary conservation, RT-PCR/in vitro splicing analysis, MutPred analysis and visual inspection of the 3D-model of the IDUA protein. Taken together, these data not only demonstrate the remarkable mutational heterogeneity characterizing type 1 mucopolysaccharidosis but also illustrate our increasing ability to make deductions pertaining to the genotype-phenotype relationship in disorders manifesting a high degree of allelic heterogeneity.

T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 372;6 nejm.org february 5, 2015

In Table 1 of this article, the ''cold-induced sweating'' row incorrectly contains a plus sign for individual CS_258 instead of a minus sign. That is, the authors did not observe cold-induced sweating for any individuals in the cohort with mutations in KLHL7. The authors apologize for the error and any confusion it may have caused.

As negative effects of the disease increased, the QoL of IMD patients and their parents decreased in terms of emotional, physical, and cognitive function. Application of expanded newborn scanning programs, early diagnosis, regular follow up, and family education would lessen the effects of the disease and improve the QoL of both families and children.

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Bisphosphonates are used for the treatment of childhood hypercalcaemia, especially that due to malignancies. Here we report the use of intravenous pamidronate for the treatment of hypercalcaemia due to vitamin D intoxication in a 3-month-old infant. Serum calcium levels were normalised without complications. Conclusion: Pamidronate may be used in hypercalcaemia due to vitamin D intoxication in paediatric cases resistant to hydration, diuretics or corticosteroids.

Based on the high frequency of hearing loss in mucopolysaccharidosis patients, early and detailed audiological evaluations are highly desirable. Therefore, regular and systematic multidisciplinary evaluations are very important.

No abstract