Gonzalez Ballesteros Luisa F, Ma Nina S, Gordon Rebecca J, Ward Leanne, Backeljauw Philippe, Wasserman Halley, Weber David R, DiMeglio Linda A, Gagne Julie, Stein Robert, Cody Declan, Simmons Kimber, Zimakas Paul, Topor Lisa Swartz, Agrawal Sungeeta, Calabria Andrew, Tebben Peter, Faircloth Ruth, Imel Erik A, Casey Linda, Carpenter Thomas O
Yale University School of Medicine, Department of Pediatrics, New Haven, CT, United States.
Boston Children's Hospital, Boston, MA, United States.
Bone. 2017 Apr;97:287-292. doi: 10.1016/j.bone.2017.02.003. Epub 2017 Feb 4.
Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases.
A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism.
Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product.
The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.
低磷血症可因饮食摄入不足、吸收不良、肾脏排泄增加或细胞内与细胞外液之间的转移而发生。我们注意到，在评估骨骼疾病的婴幼儿和儿童中，意外出现了大量特发性低磷血症病例使用氨基酸基元素配方奶粉[EF]的常见情况。我们旨在全面描述这些病例的临床特征。
随着北美和爱尔兰各中心积累的病例，对不明原因低磷血症儿童进行回顾性病历审查。分析数据以探索喂养与生化或临床特征之间的任何关系、治疗效果，并确定潜在机制。
在17家机构中识别出51名患有EF相关低磷血症的儿童。大多数儿童患有复杂疾病，在就诊前曾在不同时间段单纯喂养纽康特®配方奶粉产品。喂养方式各不相同。在评估骨折或佝偻病时检测到低磷血症。几乎所有病例均记录到碱性磷酸酶活性增加以及肾脏对磷酸盐的适当保留。骨骼X线片显示94%的病例有骨折、矿化不足或佝偻病。尽管骨骼疾病常被归因于潜在疾病，但大多数通过补充磷酸盐或更换为不同配方产品而有所改善。
观察到的生化特征表明，尽管配方奶粉成分充足，但饮食中磷的供应不足或严重吸收不良。当有可能更换为替代配方奶粉时，在引入替代配方奶粉后不久生化状态就会改善，骨骼异常最终也会改善。这些观察结果强烈表明，在某些临床情况下，配方奶粉中磷的生物利用度可能受损。这些发现的普遍性使我们强烈建议对喂养EF的儿童仔细监测矿物质代谢。应谨慎进行向替代配方奶粉的转换或实施磷酸盐补充，因为可能会发生严重低钙血症。
