BACKGROUND: Only 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. OBJECTIVE: To 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. METHODS: We 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. RESULTS: After 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. CONCLUSIONS: Despite 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.
BACKGROUND: Only 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. OBJECTIVE: To 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. METHODS: We 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. RESULTS: After 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. CONCLUSIONS: Despite 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.
Authors: Eric Villalón; Monir Shababi; Rachel Kline; Zachary C Lorson; Kyra M Florea; Christian L Lorson Journal: Hum Mol Genet Date: 2018-02-15 Impact factor: 6.150
Authors: Ellen Cottenie; Andrzej Kochanski; Albena Jordanova; Boglarka Bansagi; Magdalena Zimon; Alejandro Horga; Zane Jaunmuktane; Paola Saveri; Vedrana Milic Rasic; Jonathan Baets; Marina Bartsakoulia; Rafal Ploski; Pawel Teterycz; Milos Nikolic; Ros Quinlivan; Matilde Laura; Mary G Sweeney; Franco Taroni; Michael P Lunn; Isabella Moroni; Michael Gonzalez; Michael G Hanna; Conceicao Bettencourt; Elodie Chabrol; Andre Franke; Katja von Au; Markus Schilhabel; Dagmara Kabzińska; Irena Hausmanowa-Petrusewicz; Sebastian Brandner; Siew Choo Lim; Haiwei Song; Byung-Ok Choi; Rita Horvath; Ki-Wha Chung; Stephan Zuchner; Davide Pareyson; Matthew Harms; Mary M Reilly; Henry Houlden Journal: Am J Hum Genet Date: 2014-10-30 Impact factor: 11.025
Authors: Annie Ting Gee Chiu; Sophelia Hoi Shan Chan; Shun Ping Wu; Shun Hin Ting; Brian Hon Yin Chung; Angel On Kei Chan; Virginia Chun Nei Wong Journal: Child Neurol Open Date: 2018-04-19