What are Mucopolysaccharidoses?

Mucopolysaccharidoses (MPS) are a family of rare, hereditary disorders where lysosomal enzymes inside the cells are deficient or do not function properly. These enzymes are important in the breakdown of mucopolysaccharides or glycosaminoglycans, which are long chain molecules of sugar. When these substances are not digested properly by cell organelles called lysosomes, they accumulate inside the cells, leading to cell enlargement and dysfunction. The disorders are mostly characterized by mental retardation, liver and spleen enlargement, and skeletal deformity.

There are six types of mucopolysaccharidoses. Five of them are inherited diseases passed on to the children in an autosomal recessive pattern. Genetic disorder through autosomal recessive pattern means that for a disease to manifest in the child, both parents must have genes for the disorder. Only Hunter syndrome or MPS type II is an X-linked inheritance, which means that the defective gene is located on the sex chromosomes. Males are often affected in X-linked disorders.

MPS type I causes a deficiency in the enzyme called alpha-L-iduronidase, leading to the accumulation of dermatan sulfate and heparan sulfate in the cells. It is divided into three types, depending on the onset and severity of the disease in individuals; they are Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome. Hurler syndrome usually manifests with mental retardation during infancy. Scheie syndrome presents without nerve damage and manifests later in life, while Hurler-Scheie syndrome comes between the two ages, often with no mental retardation.

Mucopolysaccharidoses type II is called Hunter's syndrome. It causes deficiency in the enzyme iduronate sulfatase, and like MPS type I, results in the accumulation of dermatan sulfate and heparan sulfate inside the cells. Mental retardation often results, although it is generally milder compared to Hurler's syndrome.

MPS type III is divided into four subtypes, called Sanfilippo syndromes A to D. These syndromes differ in the specific enzymes involved, but mostly result in the accumulation of heparan sulfate in cells. All of them manifest with severe mental retardation, as well as other typical mucopolysaccharidoses characteristics.

Marquio syndrome, or mucopolysaccharidosis type IV, leads to a deficiency in enzyme N-acetylgalactosamine-6-sulfate sulfatase, usually resulting in the accumulation of keratan sulfate and chondroitin-6-sulfate. Unlike most other types of MPS, this syndrome is not characterized by mental retardation. There is no MPS type V.

MPS type VI is called Maroteaux Lamy syndrome. It causes deficiency in arylsulfatase B, mostly resulting in dermatan sulfate accumulation. The disorder also does not present with mental retardation, but with some spleen and liver enlargement as well as skeletal deformities and heart disease.

Sly syndrome, or mucopolysaccharidoses type VII, has a deficiency in the enzyme called B-glucoronidase, often leading to heparan sulfate and dermatan sulfate accumulation. The disorder can present at birth, in infancy, or in adulthood. Most have mental retardation, except for adult onset.