Analysis of inconsistencies in terminology of spinal and bulbar muscular atrophy and its effect on retrieval of research

Abstract

Diseases are sometimes known by many names 1–9, which complicates the retrieval of publications. Rare and emerging diseases may be especially vulnerable to this. Health sciences librarians do not often encounter rare diseases and may be unaware of the search challenges that these diseases present. To effectively retrieve publications for research, a strategy to identify all the different names of a disease is needed so that these can be incorporated into a comprehensive search. The author was engaged in a research project to create a comprehensive bibliography of the rare disease spinal and bulbar muscular atrophy (SBMA). The project utilized a strategy to identify all of the various names for the disease. This strategy should be helpful not only for SBMA researchers, but for anyone interested in a methodology for obtaining a comprehensive list of names for a disease. Spinal and bulbar muscular atrophy (SBMA) SBMA (ORPHA481, OMIM #313200, SNOMED CT Concept ID 230253001†) is a rare progressive neuromuscular disorder of males marked by proximal muscle weakness, cramping, fasciculations (twitching of individual muscle fibers), and muscle atrophy. Symptoms have been reported to first begin to develop between the third to sixth decades of life. Prevalence of SBMA has been reported alternately as 1 in 40,000 10, 1–2 in 100,000 11, and less than 1 in 50,000 live male births 12, but it is thought to be underdiagnosed 13–15. Degeneration of anterior horn cells (lower motor neurons) in the spinal cord of affected individuals is observed. Additional symptoms may include gynecomastia (abnormal growth of breasts in males), testicular atrophy, dysarthria (difficulty speaking), and dysphagia (difficulty swallowing). At this time, there is no known cure for most such neuromuscular diseases 16. Inheritance of SBMA is by traditional X-linked genetics. The disorder is related to a genetic defect in which a trinucleotide repeat occurs in the first exon of the androgen receptor gene on the X chromosome, first identified by La Spada in 1991 17. The string of three nucleotides of a trinucleotide repeat is present in a normal gene but is an unusually long string in a defective gene. The trinucleotide repeat of SBMA is cytosine-adenine-guanine (CAG), which codes for the amino acid glutamine. The presence of the repeat in DNA translation results in a string of glutamine molecules in the resulting peptide. Normal CAG repeat length in the androgen receptor gene is 11–34. SBMA is diagnosed if the number of CAG repeats exceeds 38 18, 19. Women do not develop SBMA, but heterozygous and homozygous women may exhibit mild symptoms, particularly muscle twitching and cramping 13, 20, 21. SBMA was identified as a unique disorder in 1968 by William R. Kennedy, but the disorder existed before its discovery 22. As far back as 1897, Japanese neurologist Hiroshi Kawahara first described what appeared to be SBMA in two brothers suffering from muscle atrophy and fasciculation of the tongue and limbs, with adult onset and sex-linked recessive inheritance 23, 24. Several disorders of varying severity and outcomes resemble SBMA, and the disorder is thought to be frequently misdiagnosed 25–29. The most well known is amyotrophic lateral sclerosis. The most challenging are the spinal muscular atrophies (SMA). However, SMA is an autosomal recessive genetic disease. Symptoms of most forms of SMA arise in childhood, but SMA3 is suggested to possibly first appear in adolescence or young adulthood. SMA4 symptoms may appear after age 30 30.