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Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships.

Al-Sannaa NA, Bay L, Barbouth DS, Benhayoun Y, Goizet C, Guelbert N, Jones SA, Kyosen SO, Martins AM, Phornphutkul C, Reig C, Pleat R, Fallet S, Ivanovska Holder I - Orphanet J Rare Dis (2015)

Bottom Line: Organomegaly present at onset of ERT improved in the majority of both older and younger siblings.Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress.The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points.

View Article: PubMed Central - PubMed

Affiliation: Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.

ABSTRACT

Background: Enzyme replacement therapy (ERT) with laronidase, (recombinant human α-L-iduronidase; Aldurazyme) is the primary treatment option for patients with attenuated mucopolysaccharidosis type I (MPS I). This study examined the effect of early ERT on clinical manifestations.

Methods: This multinational, retrospective case series abstracted data from records of 20 patients with Hurler-Scheie syndrome within nine sibships that included older siblings treated with laronidase after the development of significant clinical symptoms, and younger siblings treated before significant symptomatology. Median age at diagnosis was 5.6 and 0.5 years for older and younger siblings, respectively. Median age at ERT initiation was 7.9 and 1.9 years for older and younger siblings, respectively.

Results: Improvement or stabilization of somatic signs and symptoms was more notable in younger siblings. Organomegaly present at onset of ERT improved in the majority of both older and younger siblings. Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress. The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points. In general, Z-scores for younger siblings were closer to the sex- and age-matched means at follow-up.

Conclusions: These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations.

No MeSH data available.


Related in: MedlinePlus

Z-scores for height/length at T1 (time of ERT initiation) and T2 (follow-up) for older (OS) and younger siblings (YS). Group A: younger siblings ERT onset ≤1 yr of age (sibships 1-5a; Group B: younger siblings ERT onset between 2 and 4 yrs (except sibship 9 at 8.5 yr) (sibships 5b through 9)
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Fig4: Z-scores for height/length at T1 (time of ERT initiation) and T2 (follow-up) for older (OS) and younger siblings (YS). Group A: younger siblings ERT onset ≤1 yr of age (sibships 1-5a; Group B: younger siblings ERT onset between 2 and 4 yrs (except sibship 9 at 8.5 yr) (sibships 5b through 9)

Mentions: All older siblings except those from sibships 2 and 8 had Z-scores greater than two standard deviations below the mean (less than −2). At T2, Z-scores deviated further from the mean in the majority of the older siblings. Although remaining two standard deviations below the mean, in sibship 4, the Z-score improved from −3 to −2 and in sibship 9 improved from −6 to −5.6. In general, Z-scores for younger siblings at T2 were closer to sex- and age-matched means. For 6/9 of the younger siblings, Z-scores ranged from +0.88 to −1.4 at T2, and represented either improvements in height/length or no significant change from T1. For the younger siblings in sibships 6 and 9, the Z-scores at T2 were more negative than at T1 with height/length 2.5 or more standard deviations from the mean. Importantly, in all sibships (with the exception of sibship 6) the heights of the younger siblings at T2 were greater than their older siblings at comparable ages. Height/length Z-scores for all sibships at T1 and T2 are shown in Fig. 4.Fig. 4


Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships.

Al-Sannaa NA, Bay L, Barbouth DS, Benhayoun Y, Goizet C, Guelbert N, Jones SA, Kyosen SO, Martins AM, Phornphutkul C, Reig C, Pleat R, Fallet S, Ivanovska Holder I - Orphanet J Rare Dis (2015)

Z-scores for height/length at T1 (time of ERT initiation) and T2 (follow-up) for older (OS) and younger siblings (YS). Group A: younger siblings ERT onset ≤1 yr of age (sibships 1-5a; Group B: younger siblings ERT onset between 2 and 4 yrs (except sibship 9 at 8.5 yr) (sibships 5b through 9)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597395&req=5

Fig4: Z-scores for height/length at T1 (time of ERT initiation) and T2 (follow-up) for older (OS) and younger siblings (YS). Group A: younger siblings ERT onset ≤1 yr of age (sibships 1-5a; Group B: younger siblings ERT onset between 2 and 4 yrs (except sibship 9 at 8.5 yr) (sibships 5b through 9)
Mentions: All older siblings except those from sibships 2 and 8 had Z-scores greater than two standard deviations below the mean (less than −2). At T2, Z-scores deviated further from the mean in the majority of the older siblings. Although remaining two standard deviations below the mean, in sibship 4, the Z-score improved from −3 to −2 and in sibship 9 improved from −6 to −5.6. In general, Z-scores for younger siblings at T2 were closer to sex- and age-matched means. For 6/9 of the younger siblings, Z-scores ranged from +0.88 to −1.4 at T2, and represented either improvements in height/length or no significant change from T1. For the younger siblings in sibships 6 and 9, the Z-scores at T2 were more negative than at T1 with height/length 2.5 or more standard deviations from the mean. Importantly, in all sibships (with the exception of sibship 6) the heights of the younger siblings at T2 were greater than their older siblings at comparable ages. Height/length Z-scores for all sibships at T1 and T2 are shown in Fig. 4.Fig. 4

Bottom Line: Organomegaly present at onset of ERT improved in the majority of both older and younger siblings.Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress.The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points.

View Article: PubMed Central - PubMed

Affiliation: Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.

ABSTRACT

Background: Enzyme replacement therapy (ERT) with laronidase, (recombinant human α-L-iduronidase; Aldurazyme) is the primary treatment option for patients with attenuated mucopolysaccharidosis type I (MPS I). This study examined the effect of early ERT on clinical manifestations.

Methods: This multinational, retrospective case series abstracted data from records of 20 patients with Hurler-Scheie syndrome within nine sibships that included older siblings treated with laronidase after the development of significant clinical symptoms, and younger siblings treated before significant symptomatology. Median age at diagnosis was 5.6 and 0.5 years for older and younger siblings, respectively. Median age at ERT initiation was 7.9 and 1.9 years for older and younger siblings, respectively.

Results: Improvement or stabilization of somatic signs and symptoms was more notable in younger siblings. Organomegaly present at onset of ERT improved in the majority of both older and younger siblings. Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress. The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points. In general, Z-scores for younger siblings were closer to the sex- and age-matched means at follow-up.

Conclusions: These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations.

No MeSH data available.


Related in: MedlinePlus