Long-term cognitive and somatic outcomes of enzyme replacement therapy in untransplanted Hurler syndrome

Julie B Eisengart, Jeanine Jarnes, Alia Ahmed, Igor Nestrasil, Richard Ziegler, Kathleen Delaney, Elsa Shapiro, Chester Whitley, Julie B Eisengart, Jeanine Jarnes, Alia Ahmed, Igor Nestrasil, Richard Ziegler, Kathleen Delaney, Elsa Shapiro, Chester Whitley

Abstract

Mucopolysaccharidosis type I (MPS I) was added to the Recommended Uniform Screening Panel for newborn screening in 2016, highlighting recognition that early treatment of MPS I is critical to stem progressive, irreversible disease manifestations. Enzyme replacement therapy (ERT) is an approved treatment for all MPS I phenotypes, but because the severe form (MPS IH, Hurler syndrome) involves rapid neurocognitive decline, the impermeable blood-brain-barrier is considered an obstacle for ERT. Instead, hematopoietic cell transplantation (HCT) has long been recommended, as it is believed to be the only therapy that arrests neurocognitive decline. Yet ERT monotherapy has never been compared to HCT, because it is unethically unacceptable to evaluate a therapeutic alternative to one shown to treat Central Nervous System (CNS) disease. An unusual opportunity to address this question is presented with this clinical report of a 16-year-old female with MPS IH treated only with ERT since her diagnosis at age 2. Neurological functioning was stable until cervical spinal cord compression at age 8, hydrocephalus at age 11, and neurocognitive declines beginning at age 10. Somatic disease burden is significant for first degree AV block, restrictive lung disease, bilateral hearing loss, severe corneal clouding, joint pain/limitations requiring mobility assistance, and short stature. This patient's extended survival and prolonged intact neurocognitive functioning depart from the untreated natural history of MPS IH. Disease burden typically controlled by HCT emerged. Although not anticipated to provide benefit for CNS disease, ERT may have provided some amelioration or slowing of neurocognitive deterioration.

Keywords: CNS, central nervous system; Cognitive decline; ERT, Enzyme replacement therapy; Enzyme replacement therapy; HCT, hematopoietic cell transplantation; MPS I, Mucopolysaccharidosis Type I; MPS IH, Mucopolysaccharidosis Type IH, Hurler Syndrome; MPS, Mucopolysaccharidosis; MRI, magnetic resonance imaging; Mucopolysaccharidosis; Newborn screening.

Figures

Fig. 1
Fig. 1
Downward trend of IQ scores over time. This patient's IQ showed age-typical mild variability when she was a young child and stabilized to the broad average range as she aged. Her IQs began to decline when she started experiencing vision loss at 10 years old, followed by hydrocephalus at age 11. After shunting and return of vision, her IQ did not rebound the next year.

References

    1. Neufeld E., Muenzer J. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. 2001. The mucopolysaccharidoses; pp. 3421–3452.
    1. Whitley C.B. The mucopolysaccharidoses. In: Beighton P., editor. McKusick's Heritable Disorders of Connective Tissue. Mosby, Inc.; St. Louis: 1992. pp. 367–500.
    1. Shapiro E.G., Nestrasil I., Rudser K., Delaney K., Kovac V., Ahmed A., Yund B., Orchard P.J., Eisengart J., Niklason G.R. Neurocognition across the spectrum of mucopolysaccharidosis type I: age, severity, and treatment. Mol. Genet. Metab. 2015;116:61–68.
    1. Aldenhoven M., Wynn R.F., Orchard P.J., O'Meara A., Veys P., Fischer A., Valayannopoulos V., Neven B., Rovelli A., Prasad V.K. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015;125:2164–2172.
    1. Shapiro E., Lockman L., Balthazor M., Krivit W. Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J. Inherit. Metab. Dis. 1995;18:413–429.
    1. Krivit W., Peters C., Shapiro E.G. Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type III. Curr. Opin. Neurol. 1999;12:167–176.
    1. Lum S.H., Miller W.P., Jones S., Mercer J., Lund T., Bonney D., Orchard P.J., Wynn R. The changing patterns of graft failure in MPS1H, Hurler syndrome: a review of 30-years experience. Blood. 2016;128:4700.
    1. Polgreen L., Tolar J., Plog M., Himes J., Orchard P., Whitley C., Miller B., Petryk A. Growth and endocrine function in patients with Hurler syndrome after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41:1005–1011.
    1. Poe M.D., Chagnon S.L., Escolar M.L. Early treatment is associated with improved cognition in Hurler syndrome. Ann. Neurol. 2014;76:747–753.
    1. Braunlin E.A., Berry J.M., Whitley C.B. Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I. Am. J. Cardiol. 2006;98:416–418.
    1. Eisengart J.B., Shapiro E.G., Rudser K.D., Ahmed A., Kovac V., Delaney K., Mercer J., Jones S., Van der Ploeg A., Mengel K.-E. Clinical outcomes of Hurler syndrome treated exclusively with enzyme replacement therapy from a young age. Mol. Genet. Metab. 2015;114:S40.
    1. Fischl B., Salat D.H., Busa E., Albert M., Dieterich M., Haselgrove C., Van Der Kouwe A., Killiany R., Kennedy D., Klaveness S. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002;33:341–355.
    1. Kakkis E.D., Muenzer J., Tiller G.E., Waber L., Belmont J., Passage M., Izykowski B., Phillips J., Doroshow R., Walot I., Hoft R., Yu K.T., Okazaki S., Lewis D., Lachman R., Thompson J.N., Neufeld E.F. Enzyme-replacement therapy in mucopolysaccharidosis I – NEJM. N. Engl. J. Med. 2001;344:182–188.
    1. Wraith J., Beck M., Lane R., van der Ploeg A., Shapiro E., Xue Y., Kakkis E., Guffon N. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human {alpha}-L-iduronidase (laronidase) Pediatrics. 2007;120:e37.
    1. Wynn R.F., Wraith J.E., Mercer J., O'Meara A., Tylee K., Thornley M., Church H.J., Bigger B.W. Improved metabolic correction in patients with lysosomal storage disease treated with hematopoietic stem cell transplant compared with enzyme replacement therapy. J. Pediatr. 2009;154:609–611.
    1. Laraway S., Breen C., Mercer J., Jones S., Wraith James E. Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings. Mol. Genet. Metab. 2013;109:315–316.
    1. Al-Sannaa N.A., Bay L., Barbouth D.S., Benhayoun Y., Goizet C., Guelbert N., Jones S.A., Kyosen S.O., Martins A.M., Phornphutkul C. Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships. Orphanet J. Rare Dis. 2015;10:131.
    1. Gabrielli O., Clarke L.A., Bruni S., Coppa G.V. Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up. Pediatrics. 2010;125:e183–e187.
    1. Ou L., Herzog T., Koniar B.L., Gunther R., Whitley C.B. High-dose enzyme replacement therapy in murine Hurler syndrome. Mol. Genet. Metab. 2014;111:116–122.
    1. Grosse S.D., Lam W.K., Wiggins L.D., Kemper A.R. Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1. Genet. Med. 2017;19:975–982.
    1. Braunlin E.A., Harmatz P.R., Scarpa M., Furlanetto B., Kampmann C., Loehr J.P., Ponder K.P., Roberts W.C., Rosenfeld H.M., Giugliani R. Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J. Inherit. Metab. Dis. 2011;34:1183–1197.
    1. Aldenhoven M., Boelens J., de Koning T.J. The clinical outcome of Hurler syndrome after stem cell transplantation. Biol. Blood Marrow Transplant. 2008;14:485–498.
    1. Eisengart J.B., Rudser K.D., Tolar J., Orchard P.J., Kivisto T., Ziegler R.S., Whitley C.B., Shapiro E.G. Enzyme replacement is associated with better cognitive outcomes after transplant in Hurler syndrome. J. Pediatr. 2013;162:375–380.e371.
    1. Peters C., Shapiro E., Anderson J., Henslee-Downey P., Klemperer M., Cowan M., Saunders E., deAlarcon P., Twist C., Nachman J. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood. 1998;91:2601.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj