Genetics of Mucopolysaccharidosis Type III Treatment & Management
- Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD more...
No treatment for the underlying cause is available. Medical treatment is supportive and is directed toward improving the patient's quality of life. Because of the varied symptoms seen in mucopolysaccharidosis (MPS) type III, a multidisciplinary approach is indicated (see Consultations). Currently, specific therapies such as bone marrow transplantation (BMT) and enzyme replacement therapy (ERT) are not options for patients with Sanfilippo syndrome.
BMT has been shown to improve the clinical outcomes of patients with mucopolysaccharidosis disorders; however this therapy has been most successful in patients with mucopolysaccharidosis types I, II, and VI. To date, patients with mucopolysaccharidosis type III have not shown positive clinical benefit from BMT.
HSCT (hematopoietic stem cell transplantation) has shown mixed results and an unclear neurocognitive benefit.
ERT has been approved in the United States for patients with mucopolysaccharidosis types I, II, and VI. Recombinant enzymes for the deficiencies seen in mucopolysaccharidosis types IIIA and IIIB are available; however, medical trials in ERT have not been favorable in improving prognosis because the enzymes are not able to cross the blood-brain barrier to enter the CNS. Presently, enzyme injections directly into the CNS are being investigated, with clinical trials underway for mucopolysaccharidosis type IIIA and in development for mucopolysaccharidosis type IIIB.
Substrate reduction therapy (SRT), with synthetic genistein (4',5,7'-trihydroxyisoflavone) derivatives, is being investigated as a potential treatment approach in mucopolysaccharidosis. Genistein, a phytoestrogen, has shown GAG synthesis inhibition in in vitro skin fibroblasts from patients with mucopolysaccharidosis and from corresponding in vivo mouse models.
Gene therapy to treat mucopolysaccharidosis type IIIB is being researched in the United States and France using animal models.
Patients with mucopolysaccharidoses (MPSs) have greater risks for complications during general anesthesia. Complications during anesthesia have been attributed to excessive oral secretions and airway obstruction due to abnormal airway anatomy. Prior to any surgical intervention, proper precautions in regard to airway management are critical for patients with mucopolysaccharidosis.
Patients and their families require evaluation by a medical genetics team for diagnosis, counseling, up-to-date treatment options, and referrals to support groups and organizations (see Patient Education). Biological parents and their families must be offered genetic counseling to discuss the recurrence risk after the birth of an affected child.
The treatment of each patient requires consultation and ongoing care with trained pediatric specialists in the fields of neurology, ophthalmology, audiology, otolaryngology, cardiology, gastroenterology, orthopedics, and child development/child psychiatry.
Consultation with a developmental pediatrician is especially helpful in addressing behavioral concerns and to assist caregivers in establishing a sleep routine.
Pediatric surgical consultation is indicated for those patients in need of hernia repair.
Neurosurgical evaluation is indicated for those patients who show clinical signs of cervical cord compression or other nerve compression disorders (ie, claw hand deformity).
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