Mucopolysaccharidosis VI in cats – clarification regarding genetic testing

MPS VI in humans

In humans, MPS VI, or Maroteaux – Lamy syndrome (OMIM:253200), is a rare autosomal recessive LSD [19]. MPS VI is caused by homozygous or compound heterozygous mutation in ARSB (OMIM:611542) [20]. The disease has been estimated to affect 1:200,000–1,500,000 people worldwide [21]. Pathogenic variants of ARSB result in reduced or absent activity of the enzyme arylsulfatase B. The reduced activity leads to high urinary excretion and intralysosomal accumulation of large amounts of partially degraded glycosaminoglycans (GAG – previously also known as a “mucopolysaccharide” dermatan sulfate) as well as chondroitin sulfate, N-acetyl-galatosamine and N—acetylgalatosiamine-4,6-disulfate [22, 23]. GAG accumulation results in cell injury with a multi-systemic clinical picture of bone abnormalities, collectively referred to as dysostosis multiplex (disorder of the development of bone, in particular, the ossification), which affects growth, gait, and appearance.

Depending on the age of onset and progression of symptoms, patients with MPS VI have been classified into severe, intermediate, and “attenuated” forms [24]. The severe form of MPS VI is characterized by very early onset and severe progression of symptoms with various skeletal abnormalities (severe dysostosis), including dwarfism, facial dysmorphisms, and joint deformities that affect mobility. Individuals with MPS VI may develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord. Death generally occurs during childhood or adolescence.

The attenuated MPS VI form is characterized by very late onset with affected individuals living nearly normal life expectancies. Patients have been described with corneal clouding and joint stiffness [25], or mild dysostosis [26]. The intermediate form shows the middle of the spectrum of phenotypes, however, no fixed criteria for separating these descriptive categories are defined.

Since 1991, nearly 100 genetic mutations had been identified in ARSB in patients with MPS VI [20, 27–30] and are cataloged in a database (http://mps6-database.org) [31]. All types of variants can cause all severities of MPS VI and compound heterozygotes can also affect the severity of disease [28].