Mucopolysaccharidosis I (MPS I)

Hội chứng Hurler hay Mucopolysaccharidosis I (MPS I) là một bệnh rối loạn dự trữ thể tiêu bào, di truyền lặn nhiễm sắc thể thường hiếm gặp do thiếu enzyme α-L-iduronidase dẫn đến không chuyển hóa được glycosaminoglycans gây ứ đọng heparan và dermatan sulfate trong tế bào. Tỷ lệ mắc bệnh khoảng 0.99-1.99/100.000 trẻ sơ sinh đẻ sống. Điều trị thay thế bằng enzyme tái tổ hợp recombinant α-L-iduronidase (laronidase)có tác dụng cải thiện chất lượng sống cho bệnh nhân.Mục tiêu: mô tả đặc điểm lâm sàng, cận lâm sàng ở bệnh nhân MPS typ I đầu tiên được điều trị Aldurazyme thay thế tại Việt Nam.Đối tượng và phương pháp: mô tả ca bệnh: bệnh nhân nữ 4 tuổi 6 tháng được chẩn đoán MPS I dựa vào kết quả nghiên cứu lâm sàng, các xét nghiệm đo hoạt độ enzyme và phân tích gen. Bệnh nhân được điều trị truyền Aldurazyme hàng tuần với 0.58 mg/kg/tuần.Kết quả: Trẻ nữ 4 tuổi 6 tháng biểu hiện cứng khớp khi 2 tuổi, nhập viện với biểu hiện lùn, mặt thô, đục giác mạc, cứng các khớp vừa và nhỏ, biến dạng cột sống, bụng chướng, gan 3 cm dưới bờ sườn, rối loạn giấc ngủ, ngủ ngáy, hay bị viêm mũi họng. Xét nghiệm: giảm thính lực, gan to, kích thước dọc gan phải 117 mm, lách 89 mm trên siêu âm, test đi bộ 6 phút là 158,5m, α-Iduronidase 0.43 nmol/mg Prot/hrs ( normal: 41.8±15.9), glycosaminoglycan (GAG) trong nước tiểu 508.83 mg/g Creatinine (normal: 10.74~112.02), phân tích gen có đột biến dị hợp tử c.1046A>G (p.Asp349Gly) trên gen IDUA. Sau 1 năm điều trị, trẻ hoạtbát hơn, không còn ngủ ngáy, đỡ viêm mũi họng, gan lách bình thường, test đi bộ 6 phút là 1331m, GAGs niệu 61.18 mg GAGs/gCreatinine.Kết luận: Điều trị enzyme thay thế có thể cải thiện các triệu chứng lâm sàng và cải thiện chất lượng sống ở bệnh nhân MPS ITừ khóa: mucopolysaccharidosis I, Hurler, điều trị Aldurazyme trong MPS I

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Newborn Screening for Mucopolysaccharidosis I: Moving Forward Learning from Experience

International Journal of Neonatal Screening ◽

10.3390/ijns6040091 ◽

2020 ◽

Vol 6 (4) ◽

pp. 91

Author(s):

Lorne A. Clarke ◽

Patricia Dickson ◽

N. Matthew Ellinwood ◽

Terri L. Klein

Keyword(s):

Newborn Screening ◽

Predictive Value ◽

Learning From Experience ◽

Mucopolysaccharidosis I ◽

Screening Programs ◽

Screening Protocol ◽

Second Tier ◽

Mps I ◽

Recent Evaluation

There have been significant advances allowing for the integration of mucopolysaccharidosis I into newborn screening programs. Initial experiences using a single-tier approach for this disorder have highlighted shortcomings that require immediate remediation. The recent evaluation of a second-tier biomarker integrated into the MPS I newborn screening protocol has been demonstrated to greatly improve the precision and predictive value of newborn screening for this disorder. This commentary urges newborn screening programs to learn from these experiences and improve newborn screening for mucopolysaccharidosis I and future mucopolysaccharidoses newborn screening programs by implementation of a second-tier biomarker analyte.

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Mucopolysaccharidosis I (MPS I) (α-L-Iduronidase Deficiency): Hurler (MPS I-H), Hurler-Scheie (MPS I-H/S), and Scheie (MPS I-S) Syndromes

Atlas of Genetic Diagnosis and Counseling ◽

10.1007/978-1-60327-161-5_128 ◽

2007 ◽

pp. 669-677

Keyword(s):

Mucopolysaccharidosis I ◽

Mps I

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Mucopolysaccharidosis I type: new management

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2018-17-4-35-42 ◽

2019 ◽

Vol 17 (4) ◽

pp. 35-42

Author(s):

S. V. Mikhaylova ◽

A. N. Slateckay ◽

E. A. Pristanskova ◽

K. I. Kirgizov ◽

O. V. Mendelevich ◽

...

Keyword(s):

Residual Disease ◽

Upper Airway ◽

Severe Form ◽

High Rate ◽

Skeletal Deformity ◽

Hematopoietic Stem ◽

Mucopolysaccharidosis I ◽

Enzyme Replacement ◽

Idua Gene ◽

Mps I

Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2–2.5 years of age, having a high rate of success. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. This review will focus on all these critical issues related to the management of MPS I-H.

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Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells

Blood ◽

10.1182/blood-2005-02-0657 ◽

2005 ◽

Vol 106 (6) ◽

pp. 1956-1964 ◽

Cited By ~ 36

Author(s):

Chendong Pan ◽

Matthew S. Nelson ◽

Morayma Reyes ◽

Lisa Koodie ◽

Joseph J. Brazil ◽

...

Keyword(s):

Heparan Sulfate ◽

Progenitor Cells ◽

Dermatan Sulfate ◽

Hurler Syndrome ◽

Mucopolysaccharidosis I ◽

Receptor Interactions ◽

Developmental Patterning ◽

Multipotent Progenitor Cells ◽

Functional Consequences ◽

Mps I

Abstract In mucopolysaccharidosis-I (MPS-I), α-L-iduronidase deficiency leads to progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan (GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influences tissue morphogenesis by binding to and modulating the activity of several cytokines (eg, fibroblast growth factors [FGFs]) involved in developmental patterning. We recently isolated a multipotent progenitor cell from postnatal human bone marrow, which differentiates into cells of all 3 embryonic lineages. The availability of multipotent progenitor cells from healthy volunteers and patients with MPS-I (Hurler syndrome) provides a unique opportunity to directly examine the functional effects of abnormal HS on cytokine-mediated stem-cell proliferation and survival. We demonstrate here that abnormally sulfated HS in Hurler multipotent progenitor cells perturb critical FGF-2–FGFR1-HS interactions, resulting in defective FGF-2–induced proliferation and survival of Hurler multipotent progenitor cells. Both the mitogenic and survival-promoting activities of FGF-2 were restored by substitution of Hurler HS by normal HS. This perturbation of critical HS–cytokine receptor interactions may represent a mechanism by which accumulated HS contributes to the developmental pathophysiology of Hurler syndrome. Similar mechanisms may operate in the pathogenesis of other diseases where structurally abnormal GAGs accumulate.

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Cognitive Abilities of Dogs with Mucopolysaccharidosis I: Learning and Memory

Animals ◽

10.3390/ani10030397 ◽

2020 ◽

Vol 10 (3) ◽

pp. 397

Author(s):

Lena Provoost ◽

Carlo Siracusa ◽

Darko Stefanovski ◽

Yan Che ◽

Mingyao Li ◽

...

Keyword(s):

Gene Therapy ◽

Cognitive Abilities ◽

Treated Group ◽

Normal Group ◽

Cognitive Testing ◽

Mixed Effect ◽

Mucopolysaccharidosis I ◽

Clinically Normal ◽

Idua Gene ◽

Mps I

Mucopolysaccharidosis I (MPS I) results from a deficiency of a lysosomal enzyme, alpha-L-iduronidase (IDUA). IDUA deficiency leads to glycosaminoglycan (GAG) accumulation resulting in cellular degeneration and multi-organ dysfunction. The primary aims of this pilot study were to determine the feasibility of cognitive testing MPS I affected dogs and to determine their non-social cognitive abilities with and without gene therapy. Fourteen dogs were tested: 5 MPS I untreated, 5 MPS I treated, and 4 clinically normal. The treated group received intrathecal gene therapy as neonates to replace the IDUA gene. Cognitive tests included delayed non-match to position (DNMP), two-object visual discrimination (VD), reversal learning (RL), attention oddity (AO), and two-scent discrimination (SD). Responses were recorded as correct, incorrect, or no response, and analyzed using mixed effect logistic regression analysis. Significant differences were not observed among the three groups for DNMP, VD, RL, or AO. The MPS I untreated dogs were excluded from AO testing due to failing to pass acquisition of the task, potentially representing a learning or executive function deficit. The MPS I affected group (treated and untreated) was significantly more likely to discriminate between scents than the normal group, which may be due to an age effect. The normal group was comprised of the oldest dogs, and a mixed effect logistic model indicated that older dogs were more likely to respond incorrectly on scent discrimination. Overall, this study found that cognition testing of MPS I affected dogs to be feasible. This work provides a framework to refine future cognition studies of dogs affected with diseases, including MPS I, in order to assess therapies in a more comprehensive manner.

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