Rare Diseases Journal II, Sanfilippo Syndrome
This occasional feature looks at “Rare Diseases”. This designation is not an arbitrary one. In order to qualify as a rare disease, its incidence rate must affect less than 200,000 people as established by the Congress of the United States with the Orphan Drug Act of 1983.1 In fact, the legislation, in addition to creating the definition, was also instrumental in changing the entire discussion and economy around orphan drug research in the US. For example, during the ten years prior to its implementation, less than ten treatments were approved. However, since1983, the Office of Orphan Products Development (OOPD), which incentivizes research on what were previously untenable developmental costs, has been integral to bringing more than 400 new treatments to market. 1
There are believed to be upwards as many as 7,000 rare diseases according to the NIH. Within their numerous centers, one, the National Center for Advancing Translational Sciences (NCATS), studies commonalities found among populations and diseases through collaborative studies.1 From that, the following programs for rare diseases have been made available:
- Rare Diseases Clinical Research Network (RDCRN)
- Therapeutics for Rare and Neglected Diseases (TRND)
- Rare Diseases Registry Program (RaDaR)
- Genetic and Rare Diseases Information Center (GARD)
Of course, with increased and vigorous reporting, collaborations, computer models, and even communications, the designations and prevalence of rare, and in fact, all diseases may change over time.
Lysosomal storage diseases (LSDs) are genetically inherited metabolic diseases. Lysosomes are responsible for breaking down complex cellular components, like proteins, and their subsequent removal. When this process does not happen due to an enzyme deficiency, the result is a buildup of toxic cell byproducts. Lysosomal storage diseases encompass nearly 50 different diseases and can affect several areas of the body including the brain, heart, and central nervous system.2
Sanfilippo Syndrome is one of these pediatric lysosomal storage diseases, a devastatingly progressive neurodegenerative metabolic disorder affecting approximately 1 in 70,000 children. Enzymes of the lysosome, which is involved in cellular housekeeping, break down cellular material for recycling, and the enzyme involved in a specific process, heparan sulfate degradation, is lacking in individuals with this disorder.3 Their inability to break down mucopolysaccharides (also known as glycosaminoglycans or GAGs) causes an accumulation of these GAGs, which in turn then causes the cells to eventually die and subsequent brain tissue loss. This syndrome, also known as mucopolysaccharidosis (MPS) type III, is one of five autosomal recessive, neurodegenerative lysosomal storage disorders, related to incomplete heparan sulfate degradation.4 There are 4 subtypes of Sanfilippo syndrome and the morality rates, though different, are equally grim. The most common type, A, has a mean age at death (± standard deviation) of 15.22 ± 4.22 years, based on death certificates obtained from the Society of Mucopolysaccharide Diseases (UK) to better understand the natural course of these conditions, covering the years 1977-2007.5 The most common causes of death in these patients were due to pneumonia and respiratory failure.
A characterization of the disease is that it is, “like Alzheimer’s, but in children.”1 There is currently not a cure for Sanfilippo syndrome.
Here are some associated lysosomal storage disorder products that may be of interest:
Fucosidase Alpha-L- 1 Plasma, also known as FUCA1 is a member of the glycosyl hydrolase 29 family which is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Fucosidosis is an autosomal recessive lysosomal storage disease caused by the absence of alpha-L-fucosidase activity.
Alpha-galactosidase A (GLA) is a homodimeric glycoprotein which hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. GLA catalyzes the hydrolysis of melibiose into galactose and glucose. Various mutations in the GLA gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry disease (a rare lysosomal storage disorder which results from a failure to catabolize alpha-D-galactosyl glycolipid moieties).
Sialidase 1 (NEU1) is a lysosomal enzyme which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, the NEU1 enzyme is part of a heterotrimeric complex in cooperation with beta-galactosidase and cathepsin A. NEU1 gene mutations may lead to sialidosis, a lysosomal storage disease that can be the type 1 (cherry red -myoclonus syndrome or normosomatic type), which is late-onset, or the type 2 (the dysmorphic type), which takes place at an earlier age with increased acuteness.
SUMF1 is a member of the SUMF family. SUMF1 catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue called C-alpha-formylglycine. Alterations in this gene result in multiple sulfatase deficiency which is a lysosomal storage disorder.
Peptides International has services applicable to this disease, including custom peptide synthesis.