• Maria Eckart, Ulf-Peter Guenther, Jan Idkowiak, Raymonda Varon, Benjamin Grolle, Patrizia Boffi, Lionel Van Maldergem, Christoph Hübner, Markus Schuelke, and Katja von Au.
• Department of Neuropediatrics, Charité Universitätsmedizin Berlin, Berlin, Germany.
• Pediatrics. 2012 Jan 1; 129 (1): e148-56.

BackgroundOnly scarce information is available on the long-term outcome and the natural course of children with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1) due to mutations in the IGHMBP2 gene.ObjectiveTo describe the natural disease course, to systematically quantify the residual capacities of children with SMARD1 who survive on permanent mechanical respiration, and to identify markers predicting the disease outcome at the time of manifestation.MethodsWe conducted a longitudinal study of 11 infantile SMARD1 patients over a mean observational period of 7.8 (SD 3.2) years. Disease-specific features were continuously assessed by using a semiquantitative scoring system. Additionally, we analyzed the residual enzymatic activity of 6 IGHMBP2 mutants in our patients.ResultsAfter an initial rapid decline of the clinical score until the age of 2 years, residual capabilities reached a plateau or even improved. The overall clinical outcome was markedly heterogeneous, but clinical scores at the age of 3 months showed a positive linear correlation with the clinical outcome at 1 year and at 4 years of age. If expressed in an in vitro recombinant system, mutations of patients with more favorable outcomes retained residual enzymatic activity.ConclusionsDespite their severe disabilities and symptoms, most SMARD1 patients are well integrated into their home environment and two thirds of them are able to attend kindergarten or school. This information will help to counsel parents at the time of disease manifestation.

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