There is little information about MPS I-related complications during laronidase therapy. We describe the first autopsy report of a young male MPS I patient who died of infection-induced cardiopulmonary failure following 2 years of weekly treatment with laronidase.

The effects of a previously identified T364M mutation and R619G mutation on IDUA activity were examined by transfection into COS-7 cells of the IDUA cDNA construct. When compared to that of wild type cDNA, the two point mutations showed only trace amounts of IDUA activity (1.2 and 1.5% respectively, Table 2). Table 2. Expression of α- l-iduronidase in transfected COS-7 cells Transfected vector α- l-Iduronidase activity (nmol mg−1 protein−1 h−1) Total (% of wild type) pcDNA3 20.9 0.0 pcDNA3-IDUA 90.2 100.0 pcDNA3-IDUA/T364M 21.7 1.2 pcDNA3-IDUA/R619G 21.9 1.5 The activity of endogenous α- l-iduronidase in COS-7 cells was subtracted before the percentage of wild type was calculated. Efficiency of transfection was similar in all dishes by 3′ IDUA cDNA PCR amplification of transfected genomic DNA (data not shown).

5FemaleT1.40.6[c.1037 T > G] + [c.1091C > T][p.L346R] + [p.T364 M]8, 8K [44]/K [45]0.81Positive

Mucopolysaccharidosis type I: identification of novel mutations that cause Hurler/Scheie syndrome in Chinese families.

Mucopolysaccharidosis type I: identification of novel mutations that cause Hurler/Scheie syndrome in Chinese families.

KH7 Hurler/Scheie 10 – – Missense 8 CTG⇆CGG L346R

KH6 Hurler/Scheie 6 – – Missense 8 CTG⇆CGG L346R

KH3 Hurler 13 Missense 3 – – Missense 8 CTG⇆CGG L346R

KH8 Hurler 20 Insertion 6 CTGCT 704ins5 Missense 8 CTG⇆CGG L346R

KH9 Hurler 11 Insertion 6 CTGCT 704ins5 Missense 8 CTG⇆CGG L346R

KH4 Hurler 6 Insertion 6 CTGCT 704ins5 Missense 8 CTG⇆CGG L346R

while others have been shown to correlate with intermediate (T364M [13]

p.T364MACG-ATGExon 8Hurler/ ScheieMissense mutationLee-Chen et al. 1997