Sanfilippo syndrome: Year of the Zebra
Sanfilippo syndrome, also known as mucopolysaccharidosis type III, or MPS III for short, is a rare genetic metabolic disorder which causes a deficiency of an enzyme required to break down mucopolysaccharides.
Mucopolysaccharides, now known as glycosaminoglycans, are complex sugars that can be found on almost all cell membranes, and include molecules such as heparan sulfate.
These molecules are normally degraded inside the cell, where they are engulfed by lysosomes. Lysosomes then release a series of digestive enzymes.
Deficiency of one of these enzymes can prevent the breakdown of glycosaminoglycans, causing them to build up in various tissues, particularly the brain.
There are four subtypes of Sanfilippo syndrome: A, B, C and D, each resulting from a deficiency in one of the four enzymes that contribute to the breakdown of heparan sulfate.
All subtypes have an autosomal recessive inheritance, meaning an individual must inherit two mutated genes, one from each parent, to develop the disease.
Affected individuals have distinctive physical features that typically include a short stature and coarse facial features, including full lips and heavy eyebrows that meet above the nose.
Individuals may also be noted to have a large head or prominent forehead and excessive body hair growth is common. Now, clinical manifestations typically appear after the first year of life, usually between the ages of two and six.
The main characteristic seen is progressive neurological deterioration leading to childhood dementia that presents as intellectual regression, and loss of previously learned skills.
Other early symptoms can include developmental delays and speech problems. Behavioral issues are also common, including hyperactivity and disobedience or defiant behavior; as well as sleep disturbances.
Affected individuals might also present with mild skeletal or joint abnormalities, like carpal tunnel syndrome or trigger thumb.
Other signs and symptoms include recurrent sinus or respiratory infections and gastrointestinal problems, like hernias, enlargement of the liver and spleen, and chronic diarrhea.
Sometimes, there may be hearing loss and visual impairment. For individuals with Sanfilippo syndrome, life expectancy is typically around 15 to 20 years of age.
Diagnosis of Sanfilippo syndrome is usually suspected based on medical history and physical examination. The screening for Sanfilippo syndrome can be done by measuring glycosaminoglycan levels in urine or measuring enzyme activity in the blood.
The diagnosis can be confirmed through genetic testing.There is currently no cure for Sanfilippo syndrome, and treatment focuses on supportive care to manage symptoms.
Supportive care can include a multidisciplinary team approach for neurological deterioration with speech, physical, and occupational therapists; mental health professionals for psychiatric and behavioral issues; surgery for hernias; and hearing aids for hearing loss.
For parents of affected individuals, genetic counseling is recommended to discuss implications of the disease in the individual’s life and future pregnancies.
While there is no cure for Sanfilippo syndrome yet, ongoing research aims to develop several possible treatment strategies, including enzyme replacement therapy, stem cell therapy, and gene therapy.
Alright, as a quick recap, Sanfilippo syndrome is a rare genetic metabolic disorder that occurs due to a deficiency in one of the enzymes that breaks down the mucopolysaccharide heparan sulfate, leading to its build up in various tissues, particularly the brain.
The classic symptom is progressive neurological degeneration leading to childhood dementia. Diagnosis is confirmed through genetic testing.
There is no cure for Sanfilippo syndrome, and treatment is typically supportive.
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