Detection of mucopolysaccharidosis type I heterozygotes on the basis of the biochemical properties of plasma alpha-L-iduronidase.
BACKGROUND
Mucopolysaccharidosis type I (MPS I) is a disease caused by deficiency of the enzyme alpha-L-iduronidase (IDUA). Since no treatment is currently available for this disorder, the detection of heterozygotes is very important for genetic counseling and prenatal diagnosis. The objective of the present study was to characterize plasma IDUA from MPS I heterozygotes in an attempt to distinguish it from that of normal individuals.


METHODS
We determined the optimum pH, Km, Vmax and Calpha (Vmax/Km) of the reaction and the thermal stability of IDUA at 50 degrees C.


RESULTS
MPS I heterozygotes can be separated from normal individuals on the basis of Km, Calpha and thermal stability of the enzyme.


CONCLUSIONS
Taking into consideration the clinical status of the homozygous offspring, we were able to subdivide the MPS I heterozygotes into various subgroups (Hurler, Scheie or Hurler/Scheie compound), and verified that the Hurler subgroup had a lower optimum pH for IDUA activity than controls and other MPS I subgroups, and that all MPS I subgroups had higher Km and lower Calpha when compared to controls.
Mandelli
J
J
Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, RS, Porto Alegre, Brazil.
Wajner
A
A
Pires
R
R
Giugliani
R
R
Coelho
J C
JC
D004795:Enzyme Stability; D006579:Heterozygote; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007068:Iduronidase / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D008059:Mucopolysaccharidosis I / Q000097:blood* / Q000235:genetics*; D010375:Pedigree; D012016:Reference Values
D007068:Iduronidase