Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI

Furujo, Mahoko; Kubo, Toshio; Kosuga, Motomichi; Okuyama, Torayuki

doi:10.1016/j.ymgme.2011.08.029

Cited by 58 publications

(73 citation statements)

References 13 publications

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“…Overall, the length and weight increases remained slightly below normal. Our results are in-line with the previous studies of MPS VI, in which the growth rates are greater in patients below 16 years of age McGill et al 2010;Furujo et al 2011;Hendriksz et al 2013). It has been suggested that the improvement in growth is associated with the beneficial effects of the treatment on the bone cells and endocrine gland function, leading to reduced inflammation and a reduction in joint contractures .…”

Section: Discussionsupporting

confidence: 93%

Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux–Lamy Syndrome

et al. 2016

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Mucopolysaccharidosis type VI (MPS VI) is a progressive, autosomal, recessive lysosomal disorder. This disorder, due to a deficiency in N-acetylgalactosamine-4-sulfatase (ASB), results in an accumulation of glycosaminoglycan (GAG), causing multiple organ failures. In this study, monochorionic biamniotic twins with the severe form of MPS VI underwent enzyme replacement therapy (ERT) with weekly infusions of recombinant human ASB (galsulfase) at 1 mg/kg. After 9 years of ERT, a comprehensive clinical examination was performed. Several types of biochemical, immunological, and genetic investigations were also conducted. Both twins showed the typical symptoms and signs of MPS VI at baseline, including short stature, progressive dysmorphic facial features, and dysostosis multiplex. Twin 2 presented stronger multisystemic involvement, with marked musculoskeletal, neurological, and odontological components. She also developed an ischemic spinal cord lesion after surgery, which is the first case described in the literature in Maroteaux-Lamy syndrome. However, the extent of disease was found to be equally stabilized in the two sisters, concretely the cardiac and respiratory functions and body length. The early diagnosis and treatment of MPS VI are critical for an optimal clinical outcome, and further evidence for the new treatment strategies is needed.

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Section: Discussionsupporting

confidence: 93%

Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux–Lamy Syndrome

et al. 2016

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“…Aggregated data from patients who had initiated ERT when less than 5 years of age showed that over 50% of patients were below the 3rd percentile for height, although one girl was above the 97th percentile. Comparing baseline height prior to initiation of ERT to height at the end of the study, 37.5% patients remained on the same percentile growth curve, 9.4% improved to a percentile curve above and 53% fell below their original percentile curve, suggesting that growth is not normalized by ERT [63][64][65].…”

Section: Enzyme Replacement Therapy (Ert)mentioning

confidence: 99%

Therapies for the bone in mucopolysaccharidoses

Tomatsu

Barrera

Alméciga-Díaz

et al. 2015

Molecular Genetics and Metabolism

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Patients with mucopolysaccharidoses (MPS) have accumulation of glycosaminoglycans in multiple tissues which may cause coarse facial features, mental retardation, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis, leading to 1) stenosis of the upper cervical region, 2) restrictive small lung, 3) hip dysplasia, 4) restriction of joint movement, and 5) surgical complications. Patients often need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy through their lifetime. Current measures to intervene in bone disease progression are not perfect and palliative, and improved therapies are urgently required.Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzyme to bone, especially avascular cartilage, to prevent or ameliorate the devastating skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion, and damage since the severity of skeletal dysplasia is associated with level of activity during daily life.This review illustrates a current overview of therapies and their impact for bone lesions in MPS including ERT, HSCT, gene therapy, and anti-inflammatory drugs.

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“…The live birth incidence of MPS VI in Taiwan over that period, therefore, was approximately 1 in 875,000. ERT has been proven effective at reducing MPS VI symptoms (Lin et al 2010;Furujo et al 2011), and the total cost of ERT is now covered by the Taiwanese government. For Copy number of ARSB was determined for exons 3-5 using qPCR.…”

Section: Resultsmentioning

confidence: 99%

“…The incidence of MPS VI varies among different populations, ranging from 1 in 248,000 to 1 in 1,300,000 live births (Poorthuis et al 1999;Neufeld and Muenzer 2001;Pinto et al 2004;Brooks et al 2005;Lin et al 2008;Valayannopoulos et al 2010). Over the past decade, enzyme replacement therapy (ERT), using recombinant human ARSB (rhASB), has significantly improved the efficacy of treating early stages of MPS VI (Harmatz et al 2004(Harmatz et al , 2006 and similar improvements have been reported for treated patients living in Asia (Lin et al 2010;Furujo et al 2011).…”

Section: Introductionmentioning

confidence: 94%

Deletion of Exon 4 in the N-Acetylgalactosamine-4-Sulfatase Gene in a Taiwanese Patient with Mucopolysaccharidosis Type VI

Lin

Chou

et al. 2015

Tohoku J. Exp. Med.

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Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), one of the enzymes required for the degradation of dermatan sulfate (DS). Accumulation of DS in connective tissue causes growth failure, resulting in short stature. Here, we observed a 5-year-old girl who was the only one affected member of her family and who presented with an exaggerated, convex curvature of the back at the age of one year. Abnormal excretion of DS in the urine and extremely low leukocyte ARSB activity were noted. The patient was suspected to have MPS VI. Direct DNA sequencing indicated that there was no mutation in the coding region of ARSB. However, RT-PCR analysis of RNA prepared from blood samples indicated the deletion of the entire exon 4. Further analysis of the genomic DNA by quantitative PCR confirmed a homozygous deletion of exon 4, an unusual intragenic deletion in ARSB. The deletion led to a truncated protein that lacks most of the catalytic domain. The patient received recombinant human ARSB as enzyme replacement therapy (ERT) at an early stage (2 years), and responded positively in terms of skeletal development and other developmental milestones. The early identification of type VI MPS patients and subsequent treatment with ERT may be beneficial for the clinical outcome of MPS VI patients. In addition, detailed gene analysis may enhance the ability to provide genetic counseling to families of patients affected by MPS VI.

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Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI

Cited by 58 publications

References 13 publications

Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux–Lamy Syndrome

Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux–Lamy Syndrome

Therapies for the bone in mucopolysaccharidoses

Deletion of Exon 4 in the N-Acetylgalactosamine-4-Sulfatase Gene in a Taiwanese Patient with Mucopolysaccharidosis Type VI

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