History of MPS

The history of these diseases begins in the early years of the 20th century when a child was seen in the Royal Infirmary in Edinburgh. He had all the features later to become familiar as being characteristic of mucopolysaccharide storage diseases. Not knowing anything about the diseases, the physicians called it “Johnny McL’s disease”.

Then, in 1917, two patients were reported in the medical literature by Dr. Hunter from Winnipeg. Two years later a patient was recorded by Dr. Hurler in Germany. All of these patients exhibited coarse features, an enlarged liver and spleen, clawing of the hands and bony deformities. The German patient was severely developmentally delayed.

The reports by Drs. Hunter and Hurler were later read by other physicians and it became obvious that there were other children who looked like the patients and had similar characteristics. The eponym for the condition became Hurler Syndrome. Worthy of note is that the first careful description of the disease was made here in Canada.

Timeline of Discovery

Note that dates are approximate.

Hunter Syndrome first described.

Hurler Syndrome first described.

Hunter and Hurler Syndromes first recognized as being caused by a build-up of mucopolysaccharides. Prior to this, they had been thought to be caused by a build-up of lipids (fats). The term mucopolysaccharidosis is first used.

Urine from a patient with Hurler Syndrome is shown to have higher than normal levels of the mucopolysaccharides dermatan sulphate and heparan sulphate.

Sanfilippo Syndrome recognised as being a separate disease. Prior to this it had been considered as a form of Hurler Syndrome.

Scheie Syndrome is first described. Morquio syndrome is first described.

Maroteaux-Lamy Syndrome is first described.

Hunter, Hurler and Sanfilippo Syndromes were first thought to be caused by enzyme defects.

Cultured skin cells (fibroblasts) from patients with Hunter, Hurler and Sanfilippo Syndromes were shown to accumulate mucopolysaccharides (GAGs).

Co-culturing of fibroblasts from Hunter patients with fibroblasts from Hurler patients corrected this accumulation of GAGs. The enzyme defect in Hunter patients could be overcome by an enzyme present in Hurler patients, and vice versa.

Direct enzyme (Arylsulphatase 8) test for Maroteaux-Lamy is available.

Hurler and Scheie Syndromes are thought to be allelic – different mutations of the same gene.

Sanfilippo Syndrome is first sub-classified into two types, A and B. Exact enzyme defect in Hurler Syndrome is recognized as a-L-iduronidase. Enzyme defect in Hunter Syndrome is thought to be some sort of sulphatase.

Direct enzyme test is available for Hurler Syndrome. Enzyme defect in Scheie Syndrome is found to be the same as that in Hurler Syndrome. Enzyme defect in Sanfilippo B shown to be N-acetyl-glucosaminidase.

Enzyme defect in Sanfilippo A shown to be N-heparan-sulphatase. Sly Syndrome recognized and enzyme defect shown to be a-L-iduronosulphate sulphatase. First report of Hunter Syndrome affecting a girl. Direct enzyme test for Sanfilippo B available.

Direct enzyme test for Sanfilippo A available. Direct enzyme test for Hunter Syndrome available. Multiple Sulphatase Deficiency (MSD) shown to be deficient of many enzymes including idurono-sulphate sulphatase (this enzyme is deficient in Hunters syndrome), Arylsulphate A (this is deficient in Metachromatic Leukodystrophy), Arylsulphatase B (this is deficient in Maroteaux-Lamy Syndrome), Arylsulphatase C, and Cholesterol sulphatase.

Morquio syndrome sub-classified into two types- A & B. Exact enzyme defect in Morquio B found to be B-galactosidase, for which a direct enzyme test is available.

Exact enzyme defect in Morquio B is found to be N-acetyl-galactosamine 6-sulphate sulphatase. Sanfilippo type C first described. Exact enzyme defect is acetyl CoA: a-glucosamine N acetyl transferase.

Sanfilippo type D first described. Exact enzyme defect is N acetyl glucosamine 6-sulphate sulphatase.