Distress Type 1 (SMARD1) The Natural Course of Infantile Spinal Muscular Atrophy With Respiratory

abstract BACKGROUND: Only scarce information is available on the long-termoutcome and the natural course of children with infantile spinalmuscular atrophy with respiratory distress type 1 (SMARD1) due tomutations in the IGHMBP2 gene.OBJECTIVE: To describe the natural disease course, to systematicallyquantify the residual capacities of children with SMARD1 who surviveonpermanentmechanicalrespiration,andtoidentifymarkerspredict-ing the disease outcome at the time of manifestation.METHODS: We conducted a longitudinal study of 11 infantile SMARD1patients over a mean observational period of 7.8 (SD 3.2) years.Disease-specific features were continuously assessed by using asemiquantitative scoring system. Additionally, we analyzed the residualenzymatic activity of 6 IGHMBP2 mutants in our patients.RESULTS:Afteraninitialrapiddeclineoftheclinicalscoreuntiltheageof 2 years, residual capabilities reached a plateau or even improved.The overall clinical outcome was markedly heterogeneous, but clinicalscoresattheageof3monthsshowedapositivelinearcorrelationwiththe clinical outcome at 1 year and at 4 years of age. If expressed in anin vitro recombinant system, mutations of patients with more favor-able outcomes retained residual enzymatic activity.CONCLUSIONS: Despite their severe disabilities and symptoms, mostSMARD1 patients are well integrated into their home environment andtwo thirds of them are able to attend kindergarten or school. This in-formation will help to counsel parents at the time of disease manifes-tation. Pediatrics 2012;129:1–9