Sanfilippo syndrome is a hereditary disease that usually manifests between two and six years of life, causing severe health problems in the child. There is no cure yet, but there are various therapies under study.
The Sanfilippo syndrome or type III mucopolysaccharidosis (MPS III) is a rare disease with low frequency (one in 50,000 births). It is a genetic pathology of autosomal recessive transmission. Both parents must be carriers of the disease, and for the fetus to develop it, it must receive the mutated gene from each of its parents, which is summarized in a probability of 25%.
The first signs of the onset of the disease occur around two to six years of life. Until they reach that age, children have normal development. Still, from this moment, they experience a setback in what they have learned, suffer from hepatomegaly – an abnormal increase in the size of the liver -, sleep and behavior disorders, and mental retardation. The life expectancy of those affected usually reaches adolescence, although the severity of the disease is unique in each case.
The name of the pathology comes from the researcher who described it in 1962-1963, Dr. Sanfilippo, who, together with his associates, identified in eight children a series of symptoms that we now know characterize it as hepatomegaly, increased excretion of heparan sulfate in the urine, or mental retardation.
Causes of Sanfilippo syndrome
Sanfilippo Syndrome is a lysosomal storage disease caused by the absence of one of the four lysosomal hydrolases, characterized by severe central nervous system degeneration.
The lysosomes are organelles containing enzymes responsible for cell digestion. When our body lacks some of these enzymes, the material that should degrade does not accumulate in the cells, resulting in devastating effects for these and therefore for the body in general.
In the case of MPS III or Sanfilippo syndrome, the substance that accumulates is heparan sulfate, and the enzyme lacking in the cell depends on the subtype of syndrome it has, since up to four different subtypes have been described—classified as MPS III A, B, C, and D.
Symptoms and diagnosis of Sanfilippo syndrome
The clinical characteristics of Sanfilippo syndrome or type III mucopolysaccharidosis (MPS III) are severe mental defects with relatively mild somatic alterations (visceromegaly – enlargement of organs located in the abdomen, such as spleen, liver, kidneys, stomach or pancreas – and hooked hand), as well as coarse facial features.
This genetic disorder is characterized by very nonspecific signs and symptoms at the beginning of the evidence of disease, such as recurrent otitis, hepatomegaly, rhinitis, chronic diarrhea, etc., which favors the delay in the correct diagnosis of Sanfilippo syndrome.
Children affected by this syndrome may also present marked hyperactivity, destructive tendencies, and other behavioral disturbances between four and six.
Common problems in patients with Sanfilippo syndrome
The most common health problems suffered by those affected by Sanfilippo syndrome are:
- Respiratory infections, such as nasal, tonsilÂ
- Psychomotor disorders: the accumulation of mucopolysaccharides causes loss of elasticity, which implies clumsiness when walking, instability, etc.
- Hyperactivity and conduct disorders; are pretty standard and probably the most difficult to handle and cause fatigue, anxiety, and sleep disturbances.
- Repetitive diarrhea.
- Language difficulties.
- Lack of sphincter control.
Diagnosis of Sanfilippo syndrome
When the child’s parents or doctors suspect that he or she may suffer from a possible type III mucopolysaccharidosis, the first step is to perform a urine analysis (Berry test) to detect the presence of heparan sulfate in the child’s body. If the test is positive, the next step is the fibroblast analysis to identify the deficient enzyme that will determine the exact subtype of Sanfilippo syndrome.
Once this is done, it is essential to know the exact mutation to address correctly:
- Future pregnancies, since a prenatal diagnosis could be made.
- Potential therapies based on new lines of research, such as gene therapy or the best known of the chaperones – proteins that contribute to the proper functioning of other proteins.
