Study on the Development of the Therapeutic Formula for Inborn Errors of Amino Acid Metabolism Consisting of Synthetic Peptide as a Nitrogen Source

在3年期间，通过酶解乳清蛋白获得260 kg低苯丙氨酸肽（LPP），并制备由LPP作为氮源组成的PKU治疗配方1350 kg。在动物实验中，我们证实LPPs比氨基酸更快地被吸收。由于适口性和营养质量，17名患有PKU的婴幼儿接受了LPP配方奶粉治疗一年以上。其中5人已采用享有法律专业保密权的方程式超过4年。在17例服用LPP配方食品的病例中，有4例的血清苯丙氨酸（Phe）水平难以维持在8 mg/dl以下，因为100 g LPP配方食品含有69 mg Phe。在这些情况下，补充了除Phe之外的19种氨基酸的混合物。在所有这些婴儿和儿童中观察到正常生长。DQ或IQ均在正常范围内。这些病例中的血清氨基酸水平与用由氨基酸作为氮源组成的常规治疗配方治疗期间的血清氨基酸水平相容。在此之前，我们成功地有了第一例母亲苯丙酮尿症，其中一个正常的婴儿出生后，饮食治疗使用LPP配方开始在孕前时期。这名妇女预期要第二个孩子，她在怀孕前和怀孕期间接受了LPP配方奶粉和用LPP粉烹饪的固体食物。她的血液Phe水平维持在低于10 mg/dl。第二个婴儿出生时没有任何与母体PKU相关的并发症。在日本，LPP粉末和配方奶粉的开发不仅改善了PKU婴儿和儿童的预后，而且成功预防了母亲的PKU。

During the 3 year period, 260 kg of low-phenylalanine peptides (LPP) were obtained by enzymic hydrolysis of whey protein and 1350 kg of therapeutic formula for PKU consisting of LPP as a nitrogen source were prepared. In animal experiments we confirmed that LPPs were more rapidly absorbed than amino acids. Because the palatability as well as nutritional quality seventeen infants and young children with PKU were treated with LPP formula for more than one year. Five of them have been on LPP formula for more than 4 years. In four of 17 cases who have been on LPP formula serum phenylalanine (Phe) levels were difficult to maintain below 8 mg/dl because lOOg of LPP formula contain 69 mg of Phe. In those cases, a mixture of 19 kinds of amino acids except Phe were supplemented. Normal growth was observed in all these infants and children. DQ or IQ were all within the normal range. The serum ami no acid levels in these cases were compatible to those during treatment with conventional therapeutic formula consisting of amino acids as a nitrogen source. Previously, we succeeded to have the first case of maternal PKU where a normal baby was born following dietary treatment using the LPP formula started in the preconceptional period. This woman expected to have a second baby and she received LPP formula and solid food cooked with LPP powder prior to and during pregnancy. Her blood Phe levels maintained below less than 10 mg/dl. The 2nd baby was born without any complication related to the maternal PKU. Development of LPP powder and formula resulted not only a better prognosis of infants and children with PKU but also successful prevention of maternal PKU in Japan.