MPS IIID, Sanfilippo D Disease
What else is it called?
- Mucopoly-saccharidosis type 3D
- Sanfilippo syndrome D
- N-acetylglucosamine-6-sulfate sulfatase deficiency
- MPS IIID
- MPS 3D
- Glucosamine N-acetyl-6-sulfatase deficiency
- GNS deficiency
- Mucopolysaccharidosis type 3D
- Sanfilippo syndrome type D
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What causes it?
MPS IID is caused by mutations (changes) in the GNS gene. This gene provides instructions for making enzymes that are responsible for breaking down large sugar molecules called glycosaminoglycans (GAGs), formally known as mucopolysaccharides. The GNS enzyme is involved in the breakdown of heparan sulfate (a subset of GAGs).
Mutations (changes) in the GNS gene decrease or eliminate enzyme function. A lack of the enzyme disturbs the breakdown of heparan sulfate. This leads to partially broken down heparan sulfate to build up in the cells, specifically in the lysosomes.
Lysosomes are sections in the cell that digest and recycle different types of molecules. The build-up of GAGs disrupts the functions of other proteins inside the lysosomes and affects the normal functions of cells which affect the central nervous system.
How common is it?
MPS III is the most common form of mucopolysaccharidosis. MPS III (including all four types) is estimated to affect 1 in 70,000 new-borns worldwide. MPS IIIA and MPS IIB are a lot more common than MPS IIIC and MPS IIID.
What are the signs and symptoms?
Individuals with this condition may suffer from neurological symptoms including:
- Progressive (worsens with time) dementia
- Aggressive behaviour
- Hyperactivity (more active than typical)
- Loss of vision
- Inability to sleep for more than a few hours at a time
Other symptoms may include:
- Asymmetric septal hypertrophy (thick and stiff walls of the lower heart chambers)
- Coarse facial features (coarse facial appearance)
- Absent speech (absent or lack of speech development)
- Anteverted nares (upturned nasal tip/upturned nostrils)
- Coarse hair (coarse hair texture)
- Depressed nasal bridge (flat bridge of the nose)
- Diarrhoea (watery stool)
- Dysarthria (difficulty articulating speech)
- Dysphagia (poor swallowing)
- Flexion contracture (flexed joint that cannot be straightened)
- Frontal bossing (prominent, protruding forehead)
- Abnormal growth
- Hepatomegaly (enlarged liver)
- Hirsutism (excessive hairiness)
- Intellectual disability (mental deficiency)
- Joint stiffness
- Low-set ears
- Recurrent colds
- Splenomegaly (enlarged spleen)
- Thickened ribs
- Thick lower lip vermilion (increased volume of lower lip)
- Wide mouth
- Short neck
- Thick eyebrows (bushy eyebrows)
- Synophrys (mono brow/uni-brow)
* Symptoms vary from patient to patient and not all individuals with this condition will suffer from all the symptoms listed above.
How is it diagnosed?
A diagnosis of MPS IIID starts with a physical exam of the individual by a health care professional. This is usually followed by specialised urine tests as individuals with the condition will have increased levels of heparan sulfate in the urine. This will be followed by blood tests or a small skin sample to measure the enzyme activity. The decreased enzyme activity in one of the four enzymes will identify the type of MPS III (A, B, C or D).
Molecular genetic testing will confirm the diagnosis and show mutations in the GNS gene. Knowing the genetic diagnosis can be used for prenatal testing (testing a foetus while still in the womb) for future pregnancies.
Can it be treated?
There is no specific treatment for this condition. Treatment is symptomatic and supportive, aiming to manage and alleviate individual symptoms and provide support for the patients and their families.
It is important for children with this condition to be managed and supported by a multidisciplinary team of specialist to allow for the best quality of life. This could include neurologists, developmental paediatricians, metabolic specialists, orthopaedics and cardiologists.
Genetic counselling is recommended for people with this condition and their families.
Do my family need to be tested?
MPS IIID is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.
The pattern of inheritance of MPS IIID is autosomal recessive. This means that carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with MPS IIID are carriers.
When both parents are carriers, the risk to the baby in each pregnancy is
- 25% chance (1 in 4) of developing the condition
- 50% chance (1 in 2) for the baby to be a carrier of the condition
- 25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier
Genetic counselling can be requested to get a full explanation.