Eisengart Julie B, Jarnes Jeanine, Ahmed Alia, Nestrasil Igor, Ziegler Richard, Delaney Kathleen, Shapiro Elsa, Whitley Chester
Department of Pediatrics, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
College of Pharmacy, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Mol Genet Metab Rep. 2017 Sep 27;13:64-68. doi: 10.1016/j.ymgmr.2017.07.012. eCollection 2017 Dec.
Mucopolysaccharidosis type I (MPS I) was added to the Recommended Uniform Screening Panel for newborn screening in 2016, highlighting recognition that early treatment of MPS I is critical to stem progressive, irreversible disease manifestations. Enzyme replacement therapy (ERT) is an approved treatment for all MPS I phenotypes, but because the severe form (MPS IH, Hurler syndrome) involves rapid neurocognitive decline, the impermeable blood-brain-barrier is considered an obstacle for ERT. Instead, hematopoietic cell transplantation (HCT) has long been recommended, as it is believed to be the only therapy that arrests neurocognitive decline. Yet ERT monotherapy has never been compared to HCT, because it is unethically unacceptable to evaluate a therapeutic alternative to one shown to treat Central Nervous System (CNS) disease. An unusual opportunity to address this question is presented with this clinical report of a 16-year-old female with MPS IH treated only with ERT since her diagnosis at age 2. Neurological functioning was stable until cervical spinal cord compression at age 8, hydrocephalus at age 11, and neurocognitive declines beginning at age 10. Somatic disease burden is significant for first degree AV block, restrictive lung disease, bilateral hearing loss, severe corneal clouding, joint pain/limitations requiring mobility assistance, and short stature. This patient's extended survival and prolonged intact neurocognitive functioning depart from the untreated natural history of MPS IH. Disease burden typically controlled by HCT emerged. Although not anticipated to provide benefit for CNS disease, ERT may have provided some amelioration or slowing of neurocognitive deterioration.
黏多糖贮积症I型（MPS I）于2016年被纳入新生儿筛查推荐统一筛查 panel，这凸显了人们认识到MPS I的早期治疗对于阻止进行性、不可逆的疾病表现至关重要。酶替代疗法（ERT）是所有MPS I表型的一种获批治疗方法，但由于严重型（MPS IH，Hurler综合征）涉及快速的神经认知衰退，不可渗透的血脑屏障被认为是ERT的一个障碍。相反，造血细胞移植（HCT）长期以来一直被推荐，因为人们认为它是唯一能阻止神经认知衰退的疗法。然而，ERT单一疗法从未与HCT进行过比较，因为评估一种已被证明可治疗中枢神经系统（CNS）疾病的治疗替代方案在伦理上是不可接受的。这份关于一名16岁女性MPS IH患者的临床报告提供了一个解决这个问题的难得机会，该患者自2岁确诊以来仅接受ERT治疗。直到8岁出现颈脊髓压迫、11岁出现脑积水以及10岁开始出现神经认知衰退之前，神经功能一直稳定。对于一度房室传导阻滞、限制性肺病、双侧听力丧失、严重角膜混浊、需要行动辅助的关节疼痛/活动受限以及身材矮小，躯体疾病负担很重。该患者的长期存活和延长的完整神经认知功能与未治疗的MPS IH自然病程不同。通常由HCT控制的疾病负担出现了。尽管预计ERT不会对CNS疾病有益，但它可能对神经认知恶化起到了一定的改善或延缓作用。
需注意，这里的“panel”可能是有特定医学筛查相关含义的词汇，因未给出完整准确释义，所以译文直接保留了英文。
