Congenital Conditions of Hypophosphatemia in Children

Abstract

Great strides over the past few decades have increased our understanding of the pathophysiology of hypophosphatemic disorders. Phosphate is critically important to a variety of physiologic processes, including skeletal growth, development and mineralization, as well as DNA, RNA, phospholipids, and signaling pathways. Consequently, hypophosphatemic disorders have effects on multiple systems, and may cause a variety of nonspecific signs and symptoms. The acute effects of hypophosphatemia include neuromuscular symptoms and compromise. However, the dominant effects of chronic hypophosphatemia are the effects on musculoskeletal function including rickets, osteomalacia and impaired growth during childhood. While the most common causes of chronic hypophosphatemia in children are congenital, some acquired conditions also result in hypophosphatemia during childhood through a variety of mechanisms. Improved understanding of the pathophysiology of these congenital conditions has led to novel therapeutic approaches. This article will review the pathophysiologic causes of congenital hypophosphatemia, their clinical consequences and medical therapy.

Keywords: FGF23; Fibroblast growth factor 23; Hypophosphatemia; Rickets; XLH.

Figure 1.

Normal serum phosphate concentrations decrease with age during childhood. Stylized illustration adapted from the range tables provided by the Indiana University Health Pathology Laboratory (Abbreviations: Mo, month; Yr, year)

Figure 2.

Radiographs from 15-month-old male with XLH, demonstrating rachitic features in the lower limbs including metaphyseal widening, lucency, fraying, and separation from the epiphysis along with bowing deformities.