Systemic nature of spinal muscular atrophy revealed by studying insurance claims

• Published in: PloS one 2019-03, Vol.14 (3), p.e0213680-e0213680
• Main Authors: Lipnick, Scott L, Agniel, Denis M, Aggarwal, Rahul, Makhortova, Nina R, Finlayson, Samuel G, Brocato, Alexandra, Palmer, Nathan, Darras, Basil T, Kohane, Isaac, Rubin, Lee L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Aged; Analysis; Atrophy; Biology; Biology and Life Sciences; Biomarkers; Care and treatment; Cell survival; Child; Child, Preschool; Data points; Databases, Factual; Defects; Degeneration; Diagnosis; Disease Progression; Early intervention; Engineering and Technology; Female; Genes; Genetic aspects; Health; Health insurance; Hospitals; Humans; Identification methods; Infant; Infant, Newborn; Informatics; Insurance; Insurance, Health - statistics & numerical data; Logistic regression; Male; Medical schools; Medical screening; Medicine and Health Sciences; Mental disorders; Methods; Middle Aged; Muscle weakness; Muscles; Muscular atrophy; Muscular Atrophy, Spinal - diagnosis; Muscular Atrophy, Spinal - epidemiology; Muscular Atrophy, Spinal - physiopathology; Mutation; Neuromuscular diseases; Neuromuscular Diseases - diagnosis; Neuromuscular Diseases - epidemiology; Neuromuscular Diseases - physiopathology; Neurons; Odds Ratio; Patients; Phenotype; Phenotypes; Physiology; Proteins; Regression Analysis; Research and Analysis Methods; Signs and symptoms; SMN protein; Spinal muscular atrophy; Stem cells; Studies; Survival of Motor Neuron 1 Protein - genetics; Therapeutics; Time Factors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0213680

We investigated the presence of non-neuromuscular phenotypes in patients affected by Spinal Muscular Atrophy (SMA), a disorder caused by a mutation in the Survival of Motor Neuron (SMN) gene, and whether these phenotypes may be clinically detectable prior to clinical signs of neuromuscular degeneration and therefore independent of muscle weakness. We utilized a de-identified database of insurance claims to explore the health of 1,038 SMA patients compared to controls. Two analyses were performed: (1) claims from the entire insurance coverage window; and (2) for SMA patients, claims prior to diagnosis of any neuromuscular disease or evidence of major neuromuscular degeneration to increase the chance that phenotypes could be attributed directly to reduced SMN levels. Logistic regression was used to determine whether phenotypes were diagnosed at significantly different rates between SMA patients and controls and to obtain covariate-adjusted odds ratios. Results from the entire coverage window revealed a broad spectrum of phenotypes that are differentially diagnosed in SMA subjects compared to controls. Moreover, data from SMA patients prior to their first clinical signs of neuromuscular degeneration revealed numerous non-neuromuscular phenotypes including defects within the cardiovascular, gastrointestinal, metabolic, reproductive, and skeletal systems. Furthermore, our data provide evidence of a potential ordering of disease progression beginning with these non-neuromuscular phenotypes. Our data point to a direct relationship between early, detectable non-neuromuscular symptoms and SMN deficiency. Our findings are particularly important for evaluating the efficacy of SMN-increasing therapies for SMA, comparing the effectiveness of local versus systemically delivered therapeutics, and determining the optimal therapeutic treatment window prior to irreversible neuromuscular damage.