Features of Mucopolysaccharidosis Syndrome-HURLER’S SYNDROME(MPS I H, Gargoylism):
- Type- I-H
- Inheritance-Autosomal Ressesive
- Enzyme Deficiency- α-L-Iduronidase
- Stored Substrate- HS- heparan sulfate and DS-dermatan sulfate
- Clinical Features – Appears in infancy; cloudy corneas, growth retardation, reduced intelligence, coronary artery disease; rarely live 10 years.
Chromosomal abnormality on chromosome arm 4p16.3
Characterized by increased levels of MPS in urine.
- Becomes apparent in first 2 years of life, life expectancy of 6-10 yrs.
- Head appears large; facial features quite typical.
- Prominent forehead
- Broad saddle nose & wide nostrils
- Puffy eyelids with coarse bushy eyebrows
- Thick lips
- Large tongue with open mouth
- Nasal congestion & noisy breathing.
- Progressive corneal clouding classic manifestation.
- Hepatosplenomegaly, results in protrudent abdomen
- Short neck & spinal abnormalities typical.
- Flexion contractures result in “claw hand”.
- Dwarfed, mentally retarded individuals.
- Excessive accumulation of intracellular mucopolysaccarides in many tissues & organs.
- Accumulation of dermatan & heparan sulfate in cells of mononuclear – phogocyte system, fibroblasts & endothelial cells.
- Affected cells are swollen, have clear cytoplasm resulting from accumulation of PAS +ve material in engorged, vacuolated lysosomes.
- Involved fibroblasts assume appearance of ‘clear’ or ‘gargoyle’ cells.
- ‘Hurler cells’ relatively large with metachromatically staining cytoplasm with crescent shaped nuclei.
- Cells not identified with normal H/E stain but with toluidine blue or Alcian blue/ aldehyde fuchsin stains.
- Should be differentiated from mast cells.
- Shortening and broadening of the mandible with prominent gonions.
- Localized areas of bone destruction in the jaws.
- Teeth may be small and widely spaced.
- Gingival hyperplasia has been repeatedly described in
patients with Hurler syndrome.
- the tongue is also characteristically enlarged.
- Elevated levels of mucopolysaccharides in urine.
- Metachromatic granules or ‘Reily bodies’ often demonstrated in cytoplasm of circulating lymphocytes.
- Because of multisystemic involvement in patients with mucopolysaccharidosis type I (MPS I), treatment is multidisciplinary and encompasses both the curative and palliative elements.
Corrective surgery may be necessary for patients with mucopolysaccharidosis type I (MPS I) who have joint contractures or foot and hand deformities.
Corneal transplants may be required if vision problems become severe.
Given the numerous mutations at this genetic locus, identification of which allele or alleles are involved requires referral to medical geneticists for diagnosis and genetic counseling.
1.SHAFERS’s 8th edition
2.NEVIELLE’S 3rd edition