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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

Spinal radiographs from sibship 2 patients. Panel a and b show radiographs of the older sibling at age 8, after 5 years of ERT. Note the ‘S’ shaped scoliosis with right-sided convexity in the thoracic region and left-sided convexity in the lumbar region as well as gibbus deformity at L1 and L4. There is retrolisthesis of L4 with respect to L5 and possible compromise in the spinal canal at L1 and L4. Small anterior beaking is noted in the lower thoracic and lumbar vertebrae. Panel c and d are spinal radiographs of the younger sibling at age 10, after 10 years of ERT. Note the absence of spinal deformity with only minimal anterior beaking of the lower thoracolumbar vertebrae
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Fig3: Spinal radiographs from sibship 2 patients. Panel a and b show radiographs of the older sibling at age 8, after 5 years of ERT. Note the ‘S’ shaped scoliosis with right-sided convexity in the thoracic region and left-sided convexity in the lumbar region as well as gibbus deformity at L1 and L4. There is retrolisthesis of L4 with respect to L5 and possible compromise in the spinal canal at L1 and L4. Small anterior beaking is noted in the lower thoracic and lumbar vertebrae. Panel c and d are spinal radiographs of the younger sibling at age 10, after 10 years of ERT. Note the absence of spinal deformity with only minimal anterior beaking of the lower thoracolumbar vertebrae

Mentions: The younger sibling was 5 months of age at T1 and already had cardiac symptoms ranging from mild to severe (Fig. 2), and mild organomegaly. After 10 years of ERT, cardiac symptoms showed some improvement into the mild to moderate range, and organomegaly stabilized. Development remained normal. The older sibling had mild organomegaly and cardiac involvement by age 3 at T1, which remained mild with therapy. Motor development remained normal while learning difficulties present at onset of ERT persisted. Both siblings had progression of musculoskeletal symptoms, although severity remained milder in the younger sibling. Spinal radiographic findings for sibship 2 are shown in Fig. 3. Panels A and B are radiographs of the older sibling at age 8, after 5 years of ERT, showing significant scoliosis and other spinal deformities. Panels C and D are spinal radiographs of the younger sibling at age 10, after 10 years of ERT, showing the absence of spinal deformity.Fig. 3


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)

Spinal radiographs from sibship 2 patients. Panel a and b show radiographs of the older sibling at age 8, after 5 years of ERT. Note the ‘S’ shaped scoliosis with right-sided convexity in the thoracic region and left-sided convexity in the lumbar region as well as gibbus deformity at L1 and L4. There is retrolisthesis of L4 with respect to L5 and possible compromise in the spinal canal at L1 and L4. Small anterior beaking is noted in the lower thoracic and lumbar vertebrae. Panel c and d are spinal radiographs of the younger sibling at age 10, after 10 years of ERT. Note the absence of spinal deformity with only minimal anterior beaking of the lower thoracolumbar vertebrae
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Spinal radiographs from sibship 2 patients. Panel a and b show radiographs of the older sibling at age 8, after 5 years of ERT. Note the ‘S’ shaped scoliosis with right-sided convexity in the thoracic region and left-sided convexity in the lumbar region as well as gibbus deformity at L1 and L4. There is retrolisthesis of L4 with respect to L5 and possible compromise in the spinal canal at L1 and L4. Small anterior beaking is noted in the lower thoracic and lumbar vertebrae. Panel c and d are spinal radiographs of the younger sibling at age 10, after 10 years of ERT. Note the absence of spinal deformity with only minimal anterior beaking of the lower thoracolumbar vertebrae
Mentions: The younger sibling was 5 months of age at T1 and already had cardiac symptoms ranging from mild to severe (Fig. 2), and mild organomegaly. After 10 years of ERT, cardiac symptoms showed some improvement into the mild to moderate range, and organomegaly stabilized. Development remained normal. The older sibling had mild organomegaly and cardiac involvement by age 3 at T1, which remained mild with therapy. Motor development remained normal while learning difficulties present at onset of ERT persisted. Both siblings had progression of musculoskeletal symptoms, although severity remained milder in the younger sibling. Spinal radiographic findings for sibship 2 are shown in Fig. 3. Panels A and B are radiographs of the older sibling at age 8, after 5 years of ERT, showing significant scoliosis and other spinal deformities. Panels C and D are spinal radiographs of the younger sibling at age 10, after 10 years of ERT, showing the absence of spinal deformity.Fig. 3

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