Scientists provide insight into the pathology of Sanfilippo A syndrome

May 22, 2014
This is a monomer, with approximate locations of domains 1 and 2 shown. Credit: Sidhu et al.

Sanfilippo A syndrome or Mucopolysaccharidosis IIIA (MPS-IIIA) is a rare genetic lysosomal storage disease inherited from the parents of the patient. Lysosomes are the body's vehicle for breaking down many of its by-products such as proteins, nucleic acids, carbohydrates, lipids and cellular debris. The spherical vesicles are known to contain 50 different enzymes which are all active around an acidic environment of about pH 5.

Whilst each lysosomal disorder results from different gene mutations that translate into a deficiency in , they all share a common biochemical characteristic, which is when the enzyme sulfamidase is present in too small an amount or is missing completely in the cell. When this occurs, substances usually broken down by the cell as unwanted matter accumulate in the cell, leading to severe problems.

Affected children of the disease show developmental delay, behavioural abnormalities such as hyperactivity, and signs of neurodegeneration such as progressive loss of cognitive and motor functions, cerebral convulsions and spastic quadriplegia.

About 80% of the genetic alterations in sulfamidase represent replacement of single amino acids that result in functional inactive enzyme mutants. However the molecular understanding of the effects of these mutations has been confined by a lack of structural data for this enzyme.

A group of scientists from Germany and Spain have been successful in resolving the crystal structure of sulfamidase which provides convincing evidence for the molecular consequences of these amino acid replacements and is fundamental for the development of successful structure-based drug design for this devastating neurodegenerative disorder.

Key features for the successful development of novel therapeutic molecules comprise their specific activity to increase residual enzymatic activity of sulfamidase mutants and their ability to pass the blood brain barrier.

The knowledge of the structural features of sulfamidase will greatly facilitate the discovery of suitable compounds and drugs to assist in managing the disease and its debilitating effects.

Explore further: Gene therapy cures a severe paediatric neurodegenerative disease in animal models

More information: Sidhu et al, Acta Cryst. (2014), D70, 1321-1335 DOI: 10.1107/S1399004714002739

Related Stories

New therapy against rare gene defects

April 15, 2014

On 15th April is the 1st International Pompe Disease Day, a campaign to raise awareness of this rare but severe gene defect. Pompe Disease is only one of more than 40 metabolic disorders that mainly affect children under ...

Recommended for you

Researchers grow retinal nerve cells in the lab

November 30, 2015

Johns Hopkins researchers have developed a method to efficiently turn human stem cells into retinal ganglion cells, the type of nerve cells located within the retina that transmit visual signals from the eye to the brain. ...

Shining light on microbial growth and death inside our guts

November 30, 2015

For the first time, scientists can accurately measure population growth rates of the microbes that live inside mammalian gastrointestinal tracts, according to a new method reported in Nature Communications by a team at the ...

Functional human liver cells grown in the lab

November 26, 2015

In new research appearing in the prestigious journal Nature Biotechnology, an international research team led by The Hebrew University of Jerusalem describes a new technique for growing human hepatocytes in the laboratory. ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.