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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

Symptoms present at T1 for Older (OS) and Younger (YS) Siblings. Frequency of signs and symptoms at T1 was determined from a maximum of 14 possible symptoms that included coarse facial features, corneal clouding, hearing loss, sleep apnea, abnormal lung function tests, cardiac abnormalities, hepatomegaly, splenomegaly, hernia, dysostosis multiplex, joint contractures/other skeletal defects, motor developmental delay, language/cognitive delay, and restrictions in ADL
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Fig1: Symptoms present at T1 for Older (OS) and Younger (YS) Siblings. Frequency of signs and symptoms at T1 was determined from a maximum of 14 possible symptoms that included coarse facial features, corneal clouding, hearing loss, sleep apnea, abnormal lung function tests, cardiac abnormalities, hepatomegaly, splenomegaly, hernia, dysostosis multiplex, joint contractures/other skeletal defects, motor developmental delay, language/cognitive delay, and restrictions in ADL

Mentions: Figure 1 summarizes the percentages of signs and symptoms present at T1 (out of the total number of signs/symptoms assessed per patient) for all patients by sibship. Younger siblings (blue bars) generally had fewer symptoms than older siblings (red bars) at T1, particularly in Group A. All older siblings were symptomatic at T1.Fig. 1


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)

Symptoms present at T1 for Older (OS) and Younger (YS) Siblings. Frequency of signs and symptoms at T1 was determined from a maximum of 14 possible symptoms that included coarse facial features, corneal clouding, hearing loss, sleep apnea, abnormal lung function tests, cardiac abnormalities, hepatomegaly, splenomegaly, hernia, dysostosis multiplex, joint contractures/other skeletal defects, motor developmental delay, language/cognitive delay, and restrictions in ADL
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Symptoms present at T1 for Older (OS) and Younger (YS) Siblings. Frequency of signs and symptoms at T1 was determined from a maximum of 14 possible symptoms that included coarse facial features, corneal clouding, hearing loss, sleep apnea, abnormal lung function tests, cardiac abnormalities, hepatomegaly, splenomegaly, hernia, dysostosis multiplex, joint contractures/other skeletal defects, motor developmental delay, language/cognitive delay, and restrictions in ADL
Mentions: Figure 1 summarizes the percentages of signs and symptoms present at T1 (out of the total number of signs/symptoms assessed per patient) for all patients by sibship. Younger siblings (blue bars) generally had fewer symptoms than older siblings (red bars) at T1, particularly in Group A. All older siblings were symptomatic at T1.Fig. 1

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