Other ligands, such as nitric oxide and hydrogen sulfide, can also inhibit COX by binding to regulatory sites on the enzyme, reducing the rate of cellular respiration.Cyanide is a non-competitive inhibitor for COX, binding with high affinity to the partially-reduced state of the enzyme and hindering further reduction of the enzyme. In the pulsed state, cyanide binds slowly, but with high affinity. The ligand is posited to electrostatically stabilize both metals at once by positioning itself between them. A high nitric oxide concentration, such as one added exogenously to the enzyme, reverses cyanide inhibition of COX.Nitric oxide can reversibly bind to either metal ion in the binuclear center to be oxidized to nitrite. NO and CN− will compete with oxygen to bind at the site, reducing the rate of cellular respiration. Endogenous NO, however, which is produced at lower levels, augments CN− inhibition. Higher levels of NO, which correlate with the existence of more enzyme in the reduced state, lead to a greater inhibition of cyanide. At these basal concentrations, NO inhibition of Complex IV is known to have beneficial effects, such as increasing oxygen levels in blood vessel tissues. The inability of the enzyme to reduce oxygen to water results in a buildup of oxygen, which can diffuse deeper into surrounding tissues. NO inhibition of Complex IV has a larger effect at lower oxygen concentrations, increasing its utility as a vasodilator in tissues of need.Hydrogen sulfide will bind COX in a noncompetitive fashion at a regulatory site on the enzyme, similar to carbon monoxide.
Epidemiology
Incidence of Sanfilippo syndrome varies geographically, with approximately 1 case per 280,000 live births in Northern Ireland, 1 per 66,000 in Australia, and 1 per 50,000 in the Netherlands.The Australian study estimated the following incidence for each subtype of Sanfilippo syndrome:

History
The condition is named after Sylvester Sanfilippo, the pediatrician who first described the disease in 1963. Caregiver impact
Caregivers for children with Sanfilippo syndrome face a unique set of challenges because of the diseases complex nature. There is little understanding among clinicians of the family experience of caring for patients with Sanfilippo and how a caregivers experiences change and evolve as patients age. The burden and impact on caregivers quality of life is poorly defined and best-practice guidance for clinicians is lacking.A best-practice guidance to help clinicians understand the challenges caregivers face was published July 2019 in the Orphanet Journal of Rare Diseases by a group of international clinical advisors with expertise in the care of pediatric patients with Sanfilippo, lysosomal storage disorders, and life as a caregiver to a child with Sanfilippo.The group reviewed key aspects of caregiver burden associated with Sanfilippo B by identifying and quantifying the nature and impact of the disease on patients and caregivers. Recommendations were based on findings from qualitative and quantitative research.The articles authors reported, "Providing care for patients with Sanfilippo B impinges on all aspects of family life, evolving as the patient ages and the disease progresses.