Pillai Nishitha R, Elsbecker Sara A, Gupta Ashish O, Lund Troy C, Orchard Paul J, Braunlin Elizabeth
Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, MN, USA.
Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, MN, USA.
Mol Genet Metab. 2023 Nov;140(3):107669. doi: 10.1016/j.ymgme.2023.107669. Epub 2023 Jul 27.
Severe mucopolysaccharidosis type I, (MPS IH) is a rare inherited lysosomal disorder resulting in progressive storage of proteoglycans (GAGs) in central nervous system and somatic tissues and, if left untreated, causing death within the first decade of life. Hematopoietic cell transplantation (HCT) arrests many of the features of MPS IH but carries a 10-15% risk of mortality. Decreased cardiac function can occur in MPS IH and increase the risk of HCT.
Retrospective chart review was performed to determine the long-term outcome of individuals evaluated for HCT with MPS IH who had decreased cardiac function as measured by cardiac echocardiogram (echo) and ejection fraction (EF) of <50% at the time of initial evaluation.
Six patients ranging in age from 1 week to 21 months (median: 4 months) had EFs ranging from 25 to 47% (median: 32%) at diagnosis and were initiated on enzyme replacement therapy (ERT) with improvement in EF in three patients by 5 months. The remaining three patients continued to have EFs <50% and continuous milrinone infusion was added in the pre-HCT period. On average, milrinone infusion was able to be discontinued post-HCT, prior to hospital discharge, within a mean of 37 days. Five patients survived HCT and are alive today with normal EFs. One patient receiving milrinone died of sepsis during HCT with a normal EF.
Decreased cardiac systolic function in infants with MPS IH that fails to normalize with ERT alone may benefit from the addition of continuous milrinone infusion during HCT.
重型Ⅰ型黏多糖贮积症（MPS IH）是一种罕见的遗传性溶酶体疾病，导致蛋白聚糖（GAGs）在中枢神经系统和躯体组织中进行性蓄积，若不治疗，会在生命的第一个十年内死亡。造血细胞移植（HCT）可阻止MPS IH的许多特征，但有10% - 15%的死亡风险。MPS IH可出现心脏功能下降，增加HCT风险。
进行回顾性病历审查，以确定接受HCT评估的MPS IH患者的长期预后，这些患者在初次评估时经心脏超声心动图（超声）测量心脏功能下降，射血分数（EF）<50%。
6例年龄从1周龄至21个月（中位年龄：4个月）的患者在诊断时EF值为25%至47%（中位值：32%），开始接受酶替代疗法（ERT），5个月时3例患者的EF有所改善。其余3例患者的EF仍<50%，在HCT前阶段加用米力农持续输注。平均而言，米力农输注在HCT后、出院前平均37天内能够停用。5例患者HCT后存活，目前EF正常。1例接受米力农治疗的患者在HCT期间因败血症死亡，当时EF正常。
MPS IH婴儿的心脏收缩功能下降，仅ERT不能使其恢复正常，在HCT期间加用米力农持续输注可能有益。
