Mucopolysaccharidosis type 1 (Hurler/Scheie)
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A child develops coarse facial features, corneal clouding, hepatosplenomegaly, and developmental delay. Urine shows elevated dermatan and heparan sulfate.
AR; IDUA (alpha-L-iduronidase)
Spectrum:
- Hurler (severe): Onset <1 year, coarse features, corneal clouding, severe ID, cardiac disease, death by ~10 years
- Scheie (attenuated): Normal intelligence, later onset, joint stiffness, corneal clouding
- Hurler-Scheie: Intermediate
- Coarse facial features, macrocephaly
- Corneal clouding
- Hepatosplenomegaly
- Dysostosis multiplex (skeletal abnormalities)
- Cardiac valve disease
- On RUSP (some states)
- Newborn screening (some states) measures low alpha-L-iduronidase activity in dried blood spot
- Urine glycosaminoglycans: elevated dermatan sulfate and heparan sulfate
- Confirmatory: deficient alpha-L-iduronidase enzyme activity in leukocytes or fibroblasts, plus IDUA molecular testing
- HSCT (Hurler, if <2 years), enzyme replacement therapy (laronidase)
"Hur1er" = MPS Type 1: the number 1 is hidden in the name. "I did u wrong, I did (iduronidase)": alpha-L-iduronidase degrades dermatan and heparan sulfate.
Hurler has corneal clouding, unlike Hunter (MPS II), who "sees clearly and aims for X." The patient's coarse face makes you want to "hurl." Airway obstruction from glycosaminoglycan deposition in soft tissue of the neck.
Dysostosis multiplex: Malformations of Skeleton aplenty in MPS. All MPS types have bony abnormalities (thick skull, malformed vertebrae, abnormal ribs).
To differentiate MPS 1 from MPS 2, count the number of "S"s in the enzyme name: MPS 1 = 1 "S" (alpha-L-iduronidaSe); MPS 2 = 2 "S"s (iduronate-2-SulfataSe).
