Sanfilippo Syndrome, or Mucopolysaccharidosis Type III (MPS III), is a genetic disorder resulting in a form of pediatric dementia. Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a progressive disease mainly affecting the brain and spinal cord (central nervous system).
Sanfilippo syndrome, also known as Mucopolysaccharidosis type III,A is a rare, potentially lethal condition that disrupts metabolism. The rare genetic disorder is called Sanfilippo syndrome, and it is a rare genetic condition that causes deadly brain damage. Sanfilippo Syndrome develops into increased behavioral disorders, including tantrums, hyperactivity, disruptiveness, violent behavior, pica, difficulties in toilet training, and disruptions in sleep.
Many children with Sanfilippo syndrome also display autistic traits, and families frequently spend years misdiagnosing them as autism or attention deficit hyperactivity disorder. In conditions such as a rare genetic disorder, the older a child is, the worse his or her condition is, and more permanent damage is done.
It was December 2017, and Isla was nearly nine years old – the oldest child at Sanfilippo Childrens Foundation to take part in the gene therapy trials anywhere. Her involvement in the trial helped researchers learn more about a rare genetic disorder and how it reacts to gene therapy treatments, particularly for older patients.
MPS III is named after Dr. Sylvester Sanfilippo, one of the American doctors who described the condition in 1963. Sanfilippo is also part of a group of diseases called mucopolysaccharidoses (MPS), which all involve an abnormal buildup of complex sugars (called mucopolysaccharides, or GAGs, of glycosaminoglycans). Individuals with Sanfilippo Syndrome are missing, or have a malfunctioning version of, a key enzyme needed to break down long chains of sugar molecules called mucopolysaccharides, or glycosaminoglycans (GAGs). Long chains of sugar molecules called mucopolysaccharides, or glycosaminoglycans (GAGs).
Individuals with Sanfilippo syndrome are missing, or have a dysfunctional version of, a key enzyme necessary to break down long chains of sugar molecules called mucopolysaccharides, or glycosaminoglycans (GAGs ). A child born with Sanfilippo syndrome (san-fuh-LEE-po) has a defect in one of the genes that makes enzymes needed to break down heparan sulfate. Cause All four subtypes of Sanfilippo syndrome are caused by a gene change, mutation, or defect that makes it difficult for the body to break down heparan sulfate.
MPS III patients lack the enzyme needed to break down heparan sulfate, a mucopolysaccharide. A person with the condition is missing a key enzyme for breaking down a kind of waste produced by the body. Although it is possible to make the missing enzyme and provide it intravenously, it cannot cross the blood-brain barrier, and thus cannot treat the neurological symptoms of Sanfilippo syndrome.
With every pregnancy, one in four chances are the baby will inherit the recessive gene from each carrier parent and be affected by MPS III. People with MPS III typically do not show any characteristic signs of the condition at birth, but they start showing signs and symptoms of the condition during early childhood. The physical features of MPS III are less obvious than the features seen in other types of mucopolysaccharidosis.
Many of the gene therapy treatments can also help alleviate some of the symptoms of MPS III and improve an individuals quality of life. Although further studies are needed in human trials, many of these treatments have been shown to be helpful for other forms of MPS as well as neurodegenerative diseases.
The disease rate of family 1 appears to be more benign than the rates in families 2 and 3, as well as in other patients with MPS-IIID described in literature (life expectancy at 14 years and 17 years).
An autosomal recessive disorder, MPS-IIID is caused by mutations in the GNS gene (14 exons) on chromosome 12q14, which encodes N-acetylglucosamine-6-sulfatase.16,17 To date, only 4 mutations, c.1169delA,13 c.1063C > T,15 c.814C > T,14 and a large intragenic deletion,14 have been reported in patients with Sanfilippo syndrome type D. A report shows 3 novel mutations in the GNS gene and clinical follow-up of the 2 siblings described by Kaplan and Wolfe in 19877 as well as the phenotypes of 2 other unrelated families with MPS-IIID. The GNS genes are known to be involved in this genetic condition. Background Mucopolysaccharidosis type IIID (MPS-IIID), or Sanfilippo syndrome type D, is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylglucosamine-6-sulfatase gene (GNS), leading to defective degradation of heparan sulfate. The proband was a 15-year-old female of Turkish-English descent, diagnosed with Sanfilippo syndrome type D at the age of 13 years on the basis of the phenotype, a positive urinary MPS screening, and an assessment of enzymes.
A best-practice guideline that helps clinicians understand the challenges that carriers face was published July 2019 in Orphanet Journal of Rare Diseases by a panel of international clinical advisers who are experts on care for children with Sanfilippo, lysosomal storage disorders, and living as a carrier for children with Sanfilippo. A best-practice guidance to help clinicians understand the challenges caregivers face was published July 2019 in the Orphanet Journal of Rare Diseases by a group of international clinical advisors with expertise in the care of pediatric patients with Sanfilippo, lysosomal storage disorders, and life as a caregiver to a child with Sanfilippo. The participants of this first-ever study on the preferences of caretakers in relation to Sanfilippo syndrome argued in favor of clinical trials shifting focus from the main cognitive outcomes to other, more multiple-systems-related outcomes, while opinions about treatment options revealed preferences for treatment options that halt or slow progression of disorders in order to preserve current functioning to promote quality of life; therefore, parents expressed a higher tolerance of risks and desire for broader inclusion criteria in trials.