Rare genetic disorders can go undiagnosed for years as the entire spectrum of phenotypic variation is not well characterized given the reduced number of patients reported in the literature and the low frequency at which these occur. Moreover, the current paradigm for clinical diagnostics defines disease diagnosis by a specified spectrum of phenotypic findings; when such parameters are either missing, or other findings not usually observed are seen, the phenotype driven approach to diagnosis may result in a specific etiological diagnosis not even being considered within the differential diagnosis. The novel implementation of genomic sequencing approaches to investigate rare genetic disorders is allowing not only the discovery of new genes, but also the phenotypic expansion of known Mendelian genetic disorders. Here we report the detailed clinical assessment of a patient with a rare genetic disorder with undefined molecular diagnosis. We applied whole-exome sequencing to this patient and unaffected parents in order to identify the molecular cause of her disorder. We identified compound heterozygous mutations in the CTSA gene, responsible for causing galactosialidosis; the molecular diagnosis was further confirmed by biochemical studies. This report expands on the clinical spectrum of this rare lysosomal disorder and exemplifies how genomic approaches are further elucidating the characterization and understanding of genetic diseases.

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Women from all cultural groups in British North America—European, African, and Indigenous American—played a central role in medicine in early America. They acted as midwives, healers, and apothecaries and drew on a variety of cultural traditions in doing so, even as they shared many beliefs about the workings of the human body. Healing gave women a route to authority and autonomy within their social groups. As the 18th century opened, women healers were able to enter the expanding world of capitalist commerce. Anglo-American women parlayed their knowledge of herbal medicine into successful businesses, and even enslaved midwives were sometimes able to be paid in cash for their skills. However, as academic medicine took more of an interest in topics such as childbirth, women practitioners faced increasingly bitter competition from professionalizing male physicians.