Diet treatment of Galactosemic Infants: A Pilot Study

描述（由申请人提供）： 虽然经典的半乳糖血症已经认识到超过半个世纪，并与半乳糖限制饮食治疗，我们的知识是分散和不完整的障碍。一个谜是为什么饮食治疗未能预防大多数女性的言语异常、认知发育受损、神经综合征、共济失调和卵巢功能衰竭的不良后果。这种疾病的一个关键时期是新生儿期。血浆半乳糖和半乳糖醇、红细胞（RBC）半乳糖-1-磷酸、尿半乳糖醇和半乳糖酸盐的极高水平随着无半乳糖配方奶粉的建立而下降，临床症状消退。然而，异常代谢物可能需要几个月才能稳定在低水平，但仍然升高。新生儿期代谢物水平对后期长期并发症的影响尚不清楚。用于治疗半乳糖血症的新生儿的以乳糖为基础的婴儿配方食品，虽然不含游离半乳糖，但含有与大豆蛋白结合的半乳糖。生物可利用的半乳糖的量将在生命的前六个月内增加几克半乳糖负担。基本配方如Neocate完全不含半乳糖，可优选用于治疗半乳糖血症。本申请是一项随机、开放标签的初步研究，其目的是确定使用大豆配方奶粉和基础配方奶粉喂养的新生半乳糖血症婴儿的血浆、RBC和尿液中异常半乳糖代谢物水平是否存在差异。初步研究的基本原理是获得支持以下假设的数据：与含有蛋白结合半乳糖的配方食品相比，在新诊断的半乳糖血症婴儿的初始治疗中，通过减少半乳糖负荷，使用完全不含半乳糖的基本配方食品将更快地改善半乳糖中毒的生化参数，并导致血浆和尿液半乳糖醇水平降低，红细胞和尿半乳糖酸盐和RBC半乳糖-1-磷酸、半乳糖醇和半乳糖酸盐。这项研究的证据可能会对新生儿半乳糖血症的治疗产生未来的影响，并有可能减轻长期并发症。

DESCRIPTION (provided by applicant): Although classical galactosemia has been recognized for more than half a century and treated with a galactose-restricted diet, our knowledge of the disorder is fragmented and incomplete. An enigma is why the diet treatment has failed to prevent the poor outcome of speech abnormalities, impaired cognitive development, neurologic syndromes and ataxia and ovarian failure in most females. A critical time in the disorder is the neonatal period. The very high levels of plasma galactose and galactitol, red blood cell (RBC) galactose-1-phosphate, and urine galactitol and galactonate fall with institution of a galactose-free formula and clinical symptoms subside. However, it may take several months before the abnormal metabolites stabilize at a low but still elevated level. The contribution of the metabolite levels in the neonatal period to the later long-term complications is unknown. Soy-based infant formulas used in treating galactosemic newborns, though devoid of free galactose, contain galactose bound to soy protein. The amount of galactose which may be bioavailable would increase the galactose burden by several grams in the first six months of life. Elemental formulas such as Neocate are entirely galactose free and may be preferable for the treatment of galactosemia. This application is a randomized, open-label pilot study whose objective is to determine whether there is a difference in abnormal galactose metabolite levels in plasma, RBC, and urine of newborn galactosemic babies placed on a soybased and those placed on an elemental formula. The rationale for the pilot study is to obtain data to support the hypothesis that the use of an elemental formula entirely galactose free in the initial treatment of newly diagnosed galactosemic infants by reducing the galactose burden will more quickly ameliorate biochemical parameters of galactose intoxication compared to a formula containing protein bound galactose and result in lower levels of plasma and urine galactitol, red cell and urine galactonate and RBC galactose-1-phosphate, galactitol, and galactonate. Evidence from this study may have a future impact on how newborn galactosemics are treated with a potential for moderating long-term complications.