(Age and Sex Distribution) Mucopolysaccharidosis Type III is a rare congenital disorder that is present at birth. [dovemed.com]

Mucopolysaccharidosis III (Sanfilippo Syndrome)- disease presentation and experimental therapies. Pediatr Endocrinol Rev. 2014 Sep;12 Suppl 1:133-40. Review. Citation on PubMed Malm G, Månsson JE. [medlineplus.gov]

Corneal opacities, such as corneal clouding, are not usually present in individuals with MPS III. [ncbi.nlm.nih.gov]

Somatic features, such as mild organomegaly, little to no corneal clouding, and orthopedic abnormalities, may be present. Neurologic degeneration usually begins in children aged 6 years or older (sometimes even younger). [emedicine.medscape.com]

Symptoms vary greatly in this populations but some common features present in most MPSs are also present in MPS VII (course facial features, cloudy cornea, skeletal abnormalities, intellectual disabilities, etc.). [checkrare.com]

• Splenomegaly

  People with MPS III often have a slightly enlarged liver (mild hepatomegaly) or spleen (mild splenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). [medlineplus.gov]

  GAG accumulation that results in hepatomegaly and splenomegaly does not lead to dysfunction despite increases in size. Neurologic. [ncbi.nlm.nih.gov]

• Disability

  Center on Technology & Disability Designed to increase the capacity of families and providers to advocate for, acquire, and implement effective assistive and instructional technology practices, devices, and services for those who suffer from disabilities [checkrare.com]

  This condition causes progressive intellectual disability and the loss of previously acquired skills (developmental regression). [healthjade.com]

  Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities. [ncbi.nlm.nih.gov]

  […] bulge at the navel; the bulge is more visible when the baby cries or coughs Vision and hearing loss Communication difficulties Short stature Frequent incidence of pneumonia Seizures, which are mostly seen when the child reaches 10 years of age Walking disability [dovemed.com]

  This condition causes progressive intellectual disability and the loss of previously acquired skills (developmental regression or dementia). [medlineplus.gov]

• Pain

  Complications of Mucopolysaccharidosis Type III may include: Inguinal hernia causing a bulge on the side of the pubic bone, abdominal weakness, numbness in the groin, groin pain especially while coughing or lifting heavy objects Umbilical hernia causing [dovemed.com]

  Most children with the rapid onset form of MPS VI will have a lifetime of therapy and pain while those with slow onset form may not be that limited by the disease. [checkrare.com]

  Therapies may be useful, but should not be intensive, especially if they cause pain. [ncbi.nlm.nih.gov]

  […] failure 7 612964 Spermatogenic failure 8 613957 NSD1 5q35.2-q35.3 Beckwith-Wiedemann syndrome 130650 Leukemia, acute myeloid 601626 Sotos syndrome 1 117550 NSUN2 5p15.31 Mental retardation, autosomal recessive 5 611091 NTRK1 1q23.1 Insensitivity to pain [institutobernabeu.com]

• Movement Disorder

  In later stages of the disorder, people with Sanfilippo syndrome (mucopolysaccharidosis type III) may develop seizures and movement disorders. [healthjade.com]

  In later stages of the disorder, people with MPS III may develop seizures, loss of mobility, and movement disorders. The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. [medlineplus.gov]

  […] the brain and spinal cord are mostly affected, which leads to: Behavioral issues Delayed speech Anxiousness and restlessness in children Hyperactivity and aggression Lowered mental function and IQ levels, which progressively worsens Convulsions and movement [dovemed.com]

• Progressive Dementia

  Affected individuals can have severe neurological symptoms, including progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time. [rarediseases.info.nih.gov]

• Epilepsy

  AIRE 21q22.3 Autoimmune polyendocrinopathy syndrome, type I, with or without reversible metaphyseal dysplasia 240300 ALDH3A2 17p11.2 Sjogren-Larsson syndrome 270200 ALDH5A1 6p22.3 Succinic semialdehyde dehydrogenase deficiency 271980 ALDH7A1 5q23.2 Epilepsy [institutobernabeu.com]

• Hepatomegaly

  People with MPS III often have a slightly enlarged liver (mild hepatomegaly) or spleen (mild splenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). [medlineplus.gov]

  […] children Hyperactivity and aggression Lowered mental function and IQ levels, which progressively worsens Convulsions and movement disorders may develop over time Abnormally-shaped head with coarse facial features Disturbed sleep Mildly enlarged liver (hepatomegaly [dovemed.com]

  Individuals with Sanfilippo syndrome (mucopolysaccharidosis type III) typically have mildly “coarse” facial features, a large head (macrocephaly), a slightly enlarged liver (mild hepatomegaly), and a soft out-pouching around the belly-button (umbilical [healthjade.com]

  GAG accumulation that results in hepatomegaly and splenomegaly does not lead to dysfunction despite increases in size. Neurologic. [ncbi.nlm.nih.gov]

• Joint Stiffness

  Some people with MPS III have short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. [medlineplus.gov]

  However, common symptoms can include stiff joints, clouding of the cornea, and cardiac abnormalities. Management. Managing persons with MPS I is largely symptomatic and can involve multiple specialties. [checkrare.com]

  Joint stiffness or contractures and features of dysostosis multiplex are common, although much less severe than in other MPS disorders. [ncbi.nlm.nih.gov]

  Some people with Sanfilippo syndrome (mucopolysaccharidosis type III) have short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. [healthjade.com]

• Hirsutism

  Other symptoms can include coarse hair, excess hair growth (hirsutism), slightly coarse facial features, sleeping problems, mildly enlarged liver and/or spleen, speech delay, respiratory and ear infections, diarrhea, hernias, seizures and a wobbly and [rarediseases.org]

  […] delay Recurrent ear/sinus infections Large head size Diarrhea/chronic loose stool Poor sleep Speech/developmental delays “Autistic” behaviors Significant hyperactivity Respiratory issues at birth Other symptoms can be coarse hair, excess hair growth (hirsutism [healthjade.com]

  Coarse and thick hair are frequently observed, as are synophrys and hirsutism. Skin is often tough and thick, sometimes causing difficulty with venipuncture. Hepatosplenomegaly. [ncbi.nlm.nih.gov]

• Hyperactivity

  As the brain gets progressively damaged, children experience severe hyperactivity, disordered sleep, loss of speech, cognitive decline, cardiac issues, seizures, loss of mobility, and finally death, usually before adulthood. [sanfilippo.org.au]

  Sanfilippo syndrome can masquerade as ADHD (attention deficit hyperactivity disorder), autism spectrum disorder, and intellectual disability. [healthjade.com]

  Affected individuals can have severe neurological symptoms, including progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time. [rarediseases.info.nih.gov]

  Almost all affected children exhibit hyperactivity often unresponsive to medication. [ncbi.nlm.nih.gov]

  The disease can take some time to be properly diagnosed since early symptoms (speech delay, insomnia, hyperactivity, recurrent ear/sinus infections, etc.) can mimic more common conditions like attention deficit hyperactivity disorder, autism, and/or intellectual [checkrare.com]

• Behavior Problem

  Affected children often initially have delayed speech and behavior problems. [healthjade.com]

  Other symptoms include: Behavioral problems Coarse facial features Diarrhea Full lips Heavy eyebrows that meet in the middle of the face above the nose Sleep difficulties Stiff joints that may not extend fully Walking problems Clinical Trials Clinical [mpssociety.org]

  Behavioral problems often worsen with affected children becoming restless, hyperactive, destructive, anxious, impulsive, fearless, or aggressive. [medlineplus.gov]

  Behavioral problems such as hyperactivity and irritability may become obvious earlier. Severe behavioral disturbance is a very common feature of Sanfilippo syndrome, and one of the more difficult aspects of the disorder to manage. [rarediseases.org]

  problems, and sleep disturbances. [ncbi.nlm.nih.gov]

Precise identification of the specific form of Sanfilippo syndrome relies on enzymatic assays (see Workup). [emedicine.medscape.com]

Download a factsheet on Sanfilippo Treatments There is currently no treatment or cure available to children diagnosed with this devastating disease. [sanfilippo.org.au]

There is no curative treatment for MPS I but treatments are available to attenuate the progressive of the disease, including bone marrow transplantation and/or Aldurazyme (laronidase), an FDA-approved enzyme replacement therapy (ERT). [checkrare.com]

[…] care or treatment that concentrates on reducing the severity of disease symptoms. [mpssociety.org]

These can include organ-specific treatments involving corrective surgical procedures. [dovemed.com]

New directions in the treatment of Gaucher disease. Trends Pharmacol Sci. 2004 Mar;25(3):147-51. [ Links ] 39. Lukina E, Watman N, Arreguin EA, Dragosky M, Iastrebner M, Rosenbaum H, et al. [scielo.org.co]

However, the prognosis also depends upon the severity of the signs and symptoms and the subtype of MPS Type III (whether A, B, C, or D). [dovemed.com]

Prognosis Sanfilippo syndrome is a progressive disorder with a very poor prognosis. Severe CNS degeneration occurs, with progression to a vegetative state. [emedicine.medscape.com]

For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu Sanfilippo syndrome prognosis Sanfilippo syndrome has its most devastating effects on the brain. [healthjade.com]

MS/MS, allowing for the simultaneous measurement of several GAGs, provides a sensitive, specific, and reproducible GAG analysis making it potentially useful for the screening, prognosis, and monitoring of any therapeutic effect in MPS patients [9, 10] [ijponline.biomedcentral.com]

(Etiology) Mucopolysaccharidosis Type III is caused by inheriting faulty genes that prevents the body from producing certain enzymes. [dovemed.com]

Epidemiology Frequency International In 1997, Nelson reported an incidence of 1 case per 280,000 live births (0.36 cases per 100,000 live births) for Sanfilippo syndrome in Northern Ireland. [7] In 1999, Poorthuis and others reported an incidence of 4.5 [emedicine.medscape.com]

Epidemiology of lysosomal storage diseases: an overview. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS. Oxford: Oxford PharmaGenesis; 2006;Chapter 2. Clarke JTR. [rarediseases.org]

Epidemiology of Sanfilippo syndrome: results of a systematic literature review. Orphanet J Rare Dis. 2018;13:53. [ncbi.nlm.nih.gov]

Pathophysiology The clinical features of Sanfilippo syndrome, including the significant CNS component (brain and spinal cord), result from the progressive lysosomal accumulation of the GAG heparan sulfate. [5] Four enzymes are involved in the different [emedicine.medscape.com]

Lysosomal multienzyme complex: biochemistry, genetics, and molecular pathophysiology. Prog Nucleic Acid Res Mol Biol. 2001;69:81–114. Article CAS Google Scholar Wood TC, Harvey K, Beck M, Burin MG, Chien YH, Church HJ, et al. [ijponline.biomedcentral.com]

(Etiology) Mucopolysaccharidosis Type III is caused by inheriting faulty genes that prevents the body from producing certain enzymes. [dovemed.com]

The goal is to prevent and relieve suffering and to improve quality of life for people facing serious, complex illness. This includes respite care, symptom management and bereavement support and may extend over a period of time. [mpssociety.org]

Due to the inability of intravenous ERT to permeate the blood-brain barrier sufficiently to prevent neurologic disease progression, intravenous ERT has not been investigated in MPS III as intensively as it has for other lysosomal storage diseases. [ncbi.nlm.nih.gov]