Rickets is Not Always Nutritional!

Excerpt

Rickets is a common condition in children due to defective mineralization of growing bone caused by a deficiency or impaired metabolism of vitamin D, phosphorus, or calcium leading to bony deformities and stunted growth in children. While assessment of serum calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone, 1,25-dihydroxy vitamin D [1,25(OH)2D], and urinary excretion of calcium and phosphate helps in classifying and managing rickets, genetic evaluation is often needed in a subset of patients for appropriate management. Underlying genetic etiology can be either pure monogenic rickets or secondary to renal tubular dysfunction due to inherited metabolic conditions such as hereditary tyrosinemia 1 or Fanconi-Bickel syndrome. Monogenic or genetic rickets could be vitamin D-dependent rickets (VDDR) or hypophosphatemic rickets (HR), the latter being either FGF23-dependent or FGF23-independent. Depending upon the type of inheritance, genetic rickets occurs due to mono or biallelic variants in either of 20 genes (such as PHEX, FGF23, DMP1, ENPP1, SLC34A3, SLC34A1, SLC9A3R1, CLCN5, OCRL1, FGFR1, FAM20C for hypophosphatemic rickets and CYP27B1, CYP2R1, CYP3A4, VDR for vitamin D-dependent rickets). In this issue of the journal, Jacob et al. have studied 10 families with monogenic rickets at different ages with varying phenotypic severity across various genetic etiologies [1]. …