J Korean Med Sci.  2014 Feb;29(2):254-260. 10.3346/jkms.2014.29.2.254.

Impact of Enzyme Replacement Therapy on Linear Growth in Korean Patients with Mucopolysaccharidosis Type II (Hunter Syndrome)

• Cho SY
• Huh R
• Chang MS
• Lee J
• Kwun Y
• Maeng SH
• Kim SJ
• Sohn YB
• Park SW
• Kwon EK
• Han SJ
• Jung J
• Jin DK

• KMID: 1789984
• DOI: http://doi.org/10.3346/jkms.2014.29.2.254

Abstract

Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase(R)) or idursulfase beta (Hunterase(R)) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies.

Keyword

Mucopolysaccharidosis II; Hunter Syndrome; Enzyme Replacement Therapy; Growth; Elaprase; Hunterase

MeSH Terms

Adolescent
Body Height
Child
Child, Preschool
Demography
Enzyme Replacement Therapy
Humans
Iduronate Sulfatase/*therapeutic use
Infant
Male
Mild Cognitive Impairment/etiology
Mucopolysaccharidosis II/complications/diagnosis/*therapy
Mutation
Phenotype
Protein Isoforms/therapeutic use
Republic of Korea
Young Adult
Iduronate Sulfatase
Protein Isoforms

Figure

• 

  Fig. 1 Growth charts and z-scores for height for Hunter syndrome patients. (A) Growth charts for group 1 (aged less than 6 yr at initiation of ERT). (B) Growth charts for group 2 (aged 6-10 yr at initiation of ERT). (C) Growth charts for group 3 (aged 10-20 yr at initiation of ERT). (D) Z scores for group 1 (aged less than 6 yr at initiation of ERT). (E) Z scores for group 2 (aged 6-10 yr at initiation of ERT). (F) Z scores for group 3 (aged 10-20 yr at initiation of ERT). The dotted lines indicate patient growth before enzyme replacement therapy (ERT), and the continuous lines denote the growth while receiving ERT. The shaded area represents the 3rd to the 97th percentiles of height in boys based on normative data from Korean references. The red lines represent the patients with the attenuated form, and the blue lines denote those with the severe form.

• 

  Fig. 2 Yearly growth velocity and z-score of the patients with the attenuated form of groups 2 and 3. (A) Yearly growth velocity for group 2 (aged 6-10 yr at initiation of ERT). (B) Yearly growth velocity for group 3 (aged 10-20 yr at initiation of ERT). (C). Z scores for group 2 (aged 6-10 yr at initiation of ERT). (D) Z scores for group 3 (aged 10-20 yr at initiation of ERT).

• 

  Fig. 3 Regression plot showing the height z-scores before and after initiation of enzyme replacement therapy (ERT) in 17 patients aged 6-20 yr at treatment start. (A) The gray lines show the regression plot for each patient. The slope of the regression was significantly changed after the ERT compared with before the treatment (difference in z-score, 0.04; P < 0.001). (B) Impact of age at start of ERT. (C) Impact of type of mutation. (D) Impact of cognitive impairment.

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