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Detailed information of HUNTER SYNDROME
HUNTER SYNDROME
DEFINITION:
A lysosomal storage disorder characterized by the accumulation of
acid mucopolysaccharides (heparan and dermatan sulfates) in the
central nervous system and peripheral tissues.
EPIDEMIOLOGY:
- incidence: 1/100,000
- age of onset:
- risk factors:
- familial - x-linked recessive
- chrom.#: Xq27.3-q28
- gene: iduronate 2-sulfatase (IDS)
- M only
PATHOGENESIS:
- iduronate 2-sulfatase is a lysosomal enzyme which catalyzes
the breakdown of heparan sulfate (HS) and dermatan sulfate (DS)
- disease first described in 1917 by Hunter and is now
classified as Mucopolysaccharidosis Type II (MPS II)
- patients with MPS IH and MPS II excrete the same acid
mucopolysaccharides (HS and DS) yet are genotypically and
phenotypically distinct entities
2. Genetic Defect
- genetic defect -> deficiency of iduronate 2-sulfatase
activity
- incomplete degradation of heparan and dermatan sulfates ->
accumulation of HS and DS in the CNS and peripheral tissues -
two clinical variants:
- which represent the two ends of a wide spectrum of
clinical severity
CLINICAL FEATURES:
2. Behavioural Problems
- hyperactivity
- disruptive, destructive behaviour
3. Others
- moderate to severe communicating hydrocephalus with
elevated intracranial pressure after 7 years of age
- seizures
2. Musculoskeletal Manifestations
- coarse facies
- thickening of nostrils, lips, and tongue
- short neck
2. Skeletal Features
- growth retardation with short stature (dwarfism)
- mild pectus excavatum
- mild kyphosis
- progressive joint stiffening
- pes cavus
3. Other Manifestations
- upper airway obstruction
- recurrent rhinorrhea
- obstructive airway disease
- pulmonary hypertension
2. Cardiovascular
3. Gastrointestinal
- hepatomegaly/hepatosplenomegaly
- chronic diarrhea
- inguinal and umbilical hernias
4. Ophthalmologic
- clear corneas
- papilledema
- retinal pigmentation
- severe retinal degeneration with visual impairment
5. ENT
- recurrent otitis media
- progressive hearing loss
6. Cutaneous
- small nodules over the skin of the shoulders, scapulas,
posterior chest wall, and arms
2. MPS-IIB - Mild Form
- normal to mild mental retardation
2. Musculoskeletal Manifestations
- somatic manifestations may be as severe as seen in MPS-IIA
but develop at a greatly reduced rate
- carpal tunnel syndrome
3. Other Manifestations
2. Cardiovascular
- congestive heart failure (CHF)
3. Ophthalmologic
- discrete corneal opacities
- chronic papilledema
4. ENT
INVESTIGATIONS:
- deficiency of iduronate 2-sulfatase activity in leukocytes
and cultured skin fibroblasts
- prenatal
- deficiency of enzyme activity in cultured chorionic villi
or amniocytes
2. Urine
- 24 hour urine collection: elevated HS and DS
3. Imaging Studies
- large dolichocephalic skull
- thickened calvarium
2. Skull
- scaphoid
- enlarged sella with anterior excavation
3. Vertebrae
4. Long Bones
- precocious osteoarthritis of the femoral head
MANAGEMENT:
- no treatment for underlying disease
- multidisciplinary approach
- Paediatrics, Neurology, Orthopedics, ENT, Ophthalmology,
- OT, PT
- genetic counselling
2. Surgery
- surgical correction of hernias, joint contractures, carpal
tunnel syndrome, myelopathy, hydrocephalus
3. Prognosis
- life expectancy
- MPS-IIA - 10-15 years of age
- MPS-IIB - 5th - 6th decades
- death usually due to obstructive airway disease, cardiac
failure, and/or neurological complications
INTERNET LINKS:
|
Pediatric Database - HUNTER SYNDROME
Pediatric Organization - Pedbase [at] Gmail.com