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被认识到半个多世纪了，并用限制半乳糖的饮食治疗，但我们对这种疾病的了解是支离破碎和不完整的。为什么节食治疗未能防止大多数女性出现言语异常、认知发育障碍、神经综合征以及共济失调和卵巢衰竭等不良结局，这是一个谜。这种疾病的关键时期是新生儿期。随着无半乳糖配方的建立，血浆半乳糖和半乳糖醇、红细胞半乳糖-1-磷酸、尿半乳糖和半乳糖酸值的极高水平下降，临床症状减轻。然而，可能需要几个月的时间才能使异常代谢产物稳定在较低但仍处于较高水平的水平。新生儿期代谢产物水平对后期长期并发症的影响尚不清楚。用于治疗半乳糖症新生儿的大豆婴儿配方奶粉，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数量会使半乳糖的负担在生命的前六个月增加几克。元素配方，如新辛酸，是完全不含半乳糖的，可能是治疗半乳糖血症的首选。这项应用是一项随机、开放标签的初步研究，其目的是确定服用大豆配方奶粉的新生儿和服用基本配方奶粉的新生儿血浆、红细胞和尿液中异常半乳糖代谢产物水平是否存在差异。试点研究的基本原理是获得数据支持以下假设：在新诊断的半乳糖血症婴儿的初始治疗中使用完全不含半乳糖的基本配方，通过减少半乳糖负担，与含有蛋白结合半乳糖的配方相比，将更快地改善半乳糖中毒的生化参数，并导致较低的血浆和尿半乳醇、红细胞和尿半乳糖以及RBC半乳糖-1-磷酸、半乳糖醇和半乳糖酸盐水平。这项研究的证据可能会对新生儿半乳精症的治疗产生未来的影响，有可能缓解长期并发症。

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.