Sanfilippo syndrome

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Sanfilippo Syndrome Classification and external resources
ICD-10	E 76.2
ICD-9	277.5
OMIM	252900 252920 252940 252930
DiseasesDB	29177
MedlinePlus	001210
eMedicine	ped/2040
MeSH	D009084

Sanfilippo syndrome, or Mucopolysaccharidosis... 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.

1 Genetic prevalence
2 Diagnosis and Natural History
3 Treatment
4 See also
5 External links

[edit] Genetic prevalence

MPS-III has an incidence of approximately 1.89 per 100 000 live births.^{[citation needed]} Higher rates are found in certain populations such as the Ashkenazi Jews.^{[citation needed]}

Sanfilippo syndrome has an autosomal recessive pattern of inheritance.

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.

Genetics of MPS-III
MPS-III type	enzyme	gene location
MPS-III A	heparan N-sulfatase	17q25.3
MPS-III B	N-acetyl-alpha-D-glucosaminidase	17q21
MPS-III C	acetyl-CoA:alpha-glucosaminide acetyltransferase	8p11-q13
MPS-III D	N-acetylglucosamine-G-sulfate sulfatase	12q14

[edit] Diagnosis and Natural History

It should be noted that MPS-III A, B, C and D,E,F,G,H,I,J,K 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, hirsuitism and coarse hair typical of other mucopolysaccharidoses are usually not present until late in the disease. The child often develops normally initially. Acquisition of speech is often slow and incomplete. The disease then 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. Death eventually results from inanition. The life-span of an affected child does not usually extend beyond late teens to early twenties.

Although the clinical features of the disease are mainly neurological, patients may also develop diarrhea, carious teeth, and an enlarged liver and spleen. There is a broad range of clinical severity. The disease may very rarely present later in life as a psychotic episode.

The diagnosis may be confirmed by assay of enzyme levels in tissue samples and gene sequencing. Prenatal diagnosis is possible.

[edit] Treatment

Treatment remains largely supportive. The behavioural disturbances of MPS-III respond poorly to medication. If an early diagnsosis is made, bone marrow replacement may be beneficial. Although the missing enzyme can be manufactured and given intravenously, it cannot penetrate the blood-brain barrier and therefore cannot treat the neurological manifestations of the disease.

Along with many other lysosomal storage diseases, MPS-III exists as a model of a monogenetic disease involving the central nervous system. Several promising therapies are in development. Gene therapy is under investigation for MPS-III in animal models. Other potential therapies include chemical modification of deficient enzymes to allow them to penetrate the brain blood-brain barrier, stabilisation of abnormal but active enzyme to prevent its degradation, and implantation of stem cells strongly expressing the missing enzyme. For any future treatment to be successful, it must be administered as early as possible. Currently MPS-III is mainly diagnosed clinically, by which stage it is probably too late for any treatment to be very effective. Neonatal screening programs would provide the earliest possible diagnosis.