Heart Problems Less Common, Milder in Sanfilippo Than Other MPS Forms, Taiwanese Study Finds
The cardiac problems identified by the researchers included valvular heart disease due to aortic valve abnormalities and valve narrowing, which worsened with increasing age. This is consistent with the progressive nature of the disease, the investigators said.
These findings were reported in the study “Cardiac characteristics and natural progression in Taiwanese patients with mucopolysaccharidosis III,” published in the Orphanet Journal of Rare Diseases.
Mucopolysaccharidosis (MPS) is an umbrella term for a group of lysosomal storage disorders caused by genetic defects in the enzymes involved in the degradation, or breakdown, of glycosaminoglycans (GAGs) — long complex sugar molecules.
Based on the specific genetic defect presented, MPS can be categorized into seven distinct disorders that differ based on symptom onset and severity.
Cardiac problems have been described in patients with all subtypes of MPS, with exception of MPS IX, or hyaluronidase deficiency. However, few studies have focused on cardiac alterations in people with Sanfilippo syndrome, or MPS III.
Taiwanese researchers now reviewed the clinical records of 26 people with Sanfilippo syndrome, ages 1.8 to 26.5 years. Five individuals had MPS IIIA, 20 had MPS IIIB, and one had MPS IIIC. The structural characteristics and function of their hearts were determined by echocardiogram, commonly referred as cardiac echo.
Echocardiographic evaluation revealed that 10 patients (38%) had damaged or defective heart valves. A total of four (15%) patients were found to have valvular stenosis (narrowing), while eight (31%) had regurgitation (leaking heart valves).
The most prevalent cardiac valve abnormality detected was mitral valve regurgitation, which affected 31% of the patients. That was followed by aortic regurgitation in 19% of the patients. Despite the high prevalence of valvular abnormities detected, most cases were mild in severity.
No patient under the age of 4.8 years had valvular stenosis. The severity of aortic valve regurgitation, and the existence of valvular heart disease, were found to be more prevalent among older individuals.
In addition, three patients (12%) were found to have mitral valve prolapse, while five (19%) had asymmetric septal hypertrophy. Mitral valve prolapse is a condition in which the two valve flaps of the mitral valve —which lets blood flow from one chamber of the heart to another — do not close evenly. Asymmetric septal hypertrophy occurs when heart muscle cells enlarge, resulting in thicker and stiffer walls of the lower heart chambers.
The results also showed that five patients (19%) had a thickened interventricular septum — the wall separating the lower chambers of the heart. Further evaluations revealed that 11 patients (42%) also had heart arrhythmias.
“[I]t is crucial to make an early diagnosis through screening programs for high-risk populations or newborns in order to initiate ERT [enzyme replacement therapy] or gene therapy before the occurrence of irreversible cardiac damage to improve the clinical outcome,” the researchers said.
These findings and follow-up data also can be used to develop quality of care strategies for patients, they said.