Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes

Hurler syndrome is a rare autosomal recessive disorder of mucopolysaccharide metabolism. Here, we present the case of a young female patient who presented with features of respiratory distress. In addition, the patient had gingival hypertrophy, spaced dentition, misaligned eruptive permanent dentition, microdontia, coarse facial features, low set ears, depressed nasal bridge, distended abdomen, pectus carinatum, umbilical hernia and J-shaped Sella Turcica on an X-ray of the skull. A diagnosis of Hurler syndrome (Mucopolysaccharidosis Type I) was made. The patient was kept on ventilator support from the third day; however, she died on the fifth day of admission. Enzyme replacement modality of treatment can increase a patient's survival rate if an early diagnosis can be made. To the best of our knowledge, only a few cases of Hurler syndrome have been reported in Pakistan.

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Enzyme replacement in a canine model of Hurler syndrome.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.91.26.12937 ◽

1994 ◽

Vol 91 (26) ◽

pp. 12937-12941 ◽

Cited By ~ 121

Author(s):

R. M. Shull ◽

E. D. Kakkis ◽

M. F. McEntee ◽

S. A. Kania ◽

A. J. Jonas ◽

...

Keyword(s):

Canine Model ◽

Hurler Syndrome ◽

Enzyme Replacement

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Post-transplant laronidase augmentation for children with Hurler syndrome: biochemical outcomes

Scientific Reports ◽

10.1038/s41598-019-50595-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Troy C. Lund ◽

Weston P. Miller ◽

Ai Yin Liao ◽

Jakub Tolar ◽

Ryan Shanley ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Hematopoietic Cell Transplantation ◽

Residual Disease ◽

Biochemical Change ◽

Hurler Syndrome ◽

Post Transplantation ◽

Enzyme Replacement ◽

Efficacy Trials ◽

Inhibitory Antibodies ◽

Over Time

Abstract Allogeneic hematopoietic cell transplantation (HCT) benefits children with Hurler syndrome (MPS-IH). However, survivors remain burdened by substantial MPS-IH related residual disease. We studied the feasibility, safety and biochemical impact of augmentative recombinant intravenous enzyme replacement therapy (IV-ERT) post transplantation. Ten children with MPS-IH and ≥2 years from successful HCT underwent IV-ERT for 2 years’ duration. Patients were monitored for anti-drug antibody (ADA) development, including inhibitory capacity and changes in urinary excretion of glycosaminoglycans (uGAG). Three patients demonstrated low-level ADA at baseline, though all children tolerated IV-ERT well. Eight patients developed ADA over the 2-year study, with 3 (38%) meeting criteria for an inhibitory ADA response. The aggregate cohort experienced a reduction in uGAG from baseline to study end, which was enhanced in children with low or no ADA response. Conversely, children with inhibitory ADA showed increase in uGAG over time. IV-ERT in previously transplanted children with MPS-IH appears safe and can reduce uGAG, although this is reversed by the presence of inhibitory ADA. These data show a biochemical change after initiation of post-HCT IV-ERT, but the occurrence of ADA and inhibitory antibodies are a concern and should be monitored in future efficacy trials. This trial was registered at www.clinicaltrials.gov, NCT01173016, 07/30/2010.

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