Sanfilippo syndrome
| Sanfilippo syndrome | |
|---|---|
| Classification and external resources | |
| Specialty | endocrinology |
| ICD-10 | E76.2 |
| ICD-9-CM | 277.5 |
| OMIM | 252900 252920 252940 252930 |
| DiseasesDB | 29177 |
| MedlinePlus | 001210 |
| eMedicine | ped/2040 |
| MeSH | D009084 |
Sanfilippo syndrome, or mucopolysaccharidosis III (MPS-III) is a rare autosomal recessive lysosomal storage disease. It is caused by a deficiency in one of the enzymes needed to break down the glycosaminoglycan heparan sulfate (which is found in the extra-cellular matrix and on cell surface glycoproteins).
Although undegraded heparan sulfate is the primary stored substrate, glycolipids such as gangliosides are also stored despite no genetic defect in the enzymes associated with their breakdown.
The condition is named for Sylvester Sanfilippo, the pediatrician who first described the disease.
Incidence of Sanfilippo syndrome varies geographically, with approximately 1 case per 280,000 live births in Northern Ireland, 1 per 66,000 in Australia, and 1 per 50,000 in the Netherlands.
The Australian study estimated the following incidences for each subtype of Sanfilippo syndrome:
The four types of MPS-III are due to specific enzyme deficiencies affecting the breakdown of heparan sulfate, which then builds up in various organs. All four types have autosomal recessive inheritance.
MPS-III A, B, C and D are considered to be clinically indistinguishable, although mutations in different genes are responsible for each disease. The following discussion is therefore applicable to all four conditions.
The disease manifests in young children. Affected infants are apparently normal, although some mild facial dysmorphism may be noticeable. The stiff joints, hirsuteness and coarse hair typical of other mucopolysaccharidoses are usually not present until late in the disease. After an initial symptom-free interval, patients usually present with a slowing of development and/or behavioral problems, followed by progressive intellectual decline resulting in severe dementia and progressive motor disease. Acquisition of speech is often slow and incomplete. The disease progresses to increasing behavioural disturbance including temper tantrums, hyperactivity, destructiveness, aggressive behaviour, pica and sleep disturbance. As affected children have normal muscle strength and mobility, the behavioural disturbances are very difficult to manage. The disordered sleep in particular presents a significant problem to care providers. In the final phase of the illness, children become increasingly immobile and unresponsive, often require wheelchairs, and develop swallowing difficulties and seizures. The life-span of an affected child does not usually extend beyond late teens to early twenties.
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