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.

Since 2000 we have performed 54 HSCT procedures (on 44 children) for MPSIH at Manchester (Table 1). Of these, six (13.6 %) displayed significant cardiomyopathy at presentation. Interestingly three of these were from the same extended pedigree (from Kuwait), sharing the R628X IDUA gene mutation. All children were diagnosed within the first 4 months of life with dilated cardiomyopathy and significant LV functional impairment. Symptomatic cardiac failure was the predominant presenting feature in five children, with silent cardiomyopathy identified on screening echocardiography in the other. Median FS and EF at diagnosis were 12.5 % (range 3–20 %) and 35 % (15–40 %) respectively. Electrocardiography (ECG) patterns varied, but included strikingly tall QRS complexes consistent with LV enlargement/hypertrophy and evidence of myocardial ischaemia (ST segment depression; T wave inversion) in several cases. Further detailed cardiac investigation (including serum troponin) was rarely performed.

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

Supplementary TableS10