Sanfilippo Linked for 1st Time With Changes in Blood Pressure

Sanfilippo syndrome’s characteristic buildup — to toxic levels — of the complex sugar molecule heparan sulfate appears to affect the production of aldosterone, a hormone that controls blood pressure, leading to serious complications, researchers report.

They detail what is likely the first known case of this type of aldosterone deficiency, called hyperreninemic hypoaldosteronism, associated with mucopolysaccharoidosis (MPS), the group of disorders that includes Sanfilippo.

The case study, “The First Reported Case of Hyperreninemic Hypoaldosteronism Due to Mucopolysaccharidosis Disorder,” was published in the journal Cureus.

MPS disorders are characterized by deficiencies in enzymes involved in the degradation of large sugar molecules called glycosaminoglycans (GAGs) inside lysosomes, which are a cell’s digestive and recycling centers.

MPS type III, or Sanfilippo syndrome, is marked by the absence or reduced activity of one of four enzymes involved in the breakdown of a GAG called heparan sulfate, so that this molecule accumulates to levels toxic to cells.

While all cells are affected, nerve cells are particularly sensitive to heparan sulfate accumulation, and Sanfilippo is characterized by progressive and severe neurodegeneration. Sanfilippo’s four subtypes share similar signs and symptoms, with type A being the most common form.

Researchers in the U.S.reported a case of hyperreninemic hypoaldosteronism caused by an MPS — specifically, Sanfilippo syndrome.

A nine-year-old boy was admitted to a hospital’s emergency room with complaints of a lack of energy and immobility, following three months of progressive physical and mental decline. Doctors noted significant weight loss and evidence of malnutrition, developmental delays for his age, and an altered mental state. The boy also had low blood pressure, and a slightly low heart rate.

Lab work found liver and kidney failure, impaired blood clotting, low blood cell counts, higher-than-normal levels of sodium in the blood, and the presence of urea in the blood, requiring dialysis.

Further examination and testing identified coarse facial features, generalized brain shrinkage, contractures in all major joints, bone abnormalities, and severe aortic insufficiency — all suggestive of an MPS. Aortic insufficiency refers to problems with a heart valve, allowing blood to flow in the wrong direction.

This potential diagnosis, also supported by the detection of GAG deposits in the bone marrow, was confirmed by genetic testing. The boy had Sanfilippo type A.

During a second month of hospitalization, he developed higher-than-normal levels of potassium in the blood (hyperkalemia). Further blood work revealed lower levels of aldosterone, high levels of renin (a molecule produced by the kidneys to increase blood pressure), and normal cortisol levels.

Aldosterone is a hormone involved in the regulation of sodium and potassium levels in the blood, controlling blood pressure. Along with aldosterone, cortisol is one of the hormones produced by the adrenal glands, located above the kidneys.

This supported a diagnosis of hyperreninemic hypoaldosteronism, which is characterized by low sodium and high potassium levels, and abnormal blood pressure. In the boy’s case, aldosterone’s lack was not likely related to adrenal gland insufficiency, the researchers reported. Rather, they suspected it resulted from either damage in the specific region responsible for aldosterone production, or to molecular signaling problems.

Given that heparan sulfate normally acts as a storage site of basic fibroblast growth factor (bFGF), an activator of aldosterone production, the scientists suggested that the formation of heparan sulfate deposits in Sanfilippo syndrome may trap bFGF, reducing the signaling that induces aldosterone. The resulting deficiency leads to low blood pressure.

The boy’s potassium levels eventually stabilized with appropriate treatment, suggesting a gradual recovery of aldosterone.

“To our knowledge, this is the first reported case of hyperreninemic hypoaldosteronism caused by an MPS disorder,” the researchers wrote, adding that this type of aldosterone deficiency “should be considered in the differential diagnosis of a patient with hyperkalemia and an MPS disorder.”