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Published in Anton Sebastian, A Dictionary of the History of Medicine, 2018
Gargoylism or Hurler Syndrome A hereditary disease due to a disturbance of mucopolysaccharide metabolism. Described in 1917 in two brothers by a Canadian professor of medicine, Charles Hunter (1872–1955). Further features, including corneal opacity and mental retardation, were observed in 1919 in two infants by German pediatrician, Gertrude Hurler.
Mucopolysaccharidosis Type I and Bilateral Optic Disc Edema
Published in Neuro-Ophthalmology, 2019
Sean M. Gratton, Thanuja Neerukonda
Mucopolysaccharidosis type I (MPS I or Hurler syndrome) is a multisystem genetic disorder caused by α-L-iduronidase (IDUA) deficiency, which leads to widespread accumulation of glycosaminoglycans triggering tissue damage and organ dysfunction. Symptoms mostly start in the first year of life and include upper airway obstruction, laryngeal and tracheal narrowing, hearing and visual deficits, skeletal deformities, organomegaly, abdominal herniae, and progressive neurological disease with severe cognitive delay.1 A variety of ocular manifestations have been described in Hurler Syndrome including decreased visual acuity and high hyperopia,2 abnormal corneal hysteresis,3 and optic nerve head swelling and optic atrophy.4 Other mucopolysaccharidoses have ocular manifestations as well including diffuse fine corneal deposits, pigmentary retinal degeneration, pseudopapilledema, and macular-edema.5 The authors present the case of an 11-year-old boy with Hurler Syndrome and optic disc edema related to ocular glycosaminoglycan deposition.
An update on gene therapy for lysosomal storage disorders
Published in Expert Opinion on Biological Therapy, 2019
Murtaza S. Nagree, Simone Scalia, William M. McKillop, Jeffrey A. Medin
As the safety of various gene therapy platforms is demonstrated, we need to begin placing deeper focus on evaluation of efficacy. While patient-reported outcomes must be closely monitored, some attention must also be paid to the search for useful biomarkers, which will likely vary with each LSD. Transduction/editing efficiencies can be assayed by vector copy number and qPCR assays, transgene function can be followed by enzyme activity assays, and substrate levels can be tracked in appropriate tissues. However, monitoring substrate levels may not be fully informative of disease state, as exemplified by the dissociation of substrate levels and severity of disease presentation in Fabry patients [149]. This is not only important in lieu of gene therapy as a treatment, but also from an ethical perspective. Prolongation of lifespan is often considered the most important metric in pre-clinical studies. However, prolonging life at the expense of quality-of-life must be carefully considered, with decisions made by health-care practitioners that are well informed of the underlying biology of their disease of interest. For example, if treatment of children with severe MPS I (Hurler syndrome) is not fully efficacious the disorder may be converted to an attenuated form, leaving children suffering long term with severe neural or other disabilities.
Best Interest, Harm, God’s Will, Parental Discretion, or Utility
Published in The American Journal of Bioethics, 2018
In his book Children, Ethics, & Modern Medicine, theologian Richard Miller (2003) tells of one such tough case that illustrates the problem. Billy, a boy with Hurler syndrome, underwent a bone marrow transplant at age 13 months. The transplant failed to engraft. His disease progressed. When he was four, his parents sought another transplant. The chance of a second transplant being beneficial was very low. Billy’s second transplant engrafted, but he developed graft-versus-host disease, sepsis, and multisystem organ failure. He remained on mechanical ventilation, vasopressors, and dialysis for weeks. The doctors recommended withdrawal of life-support. The parents did not agree.