Pathak PP, Ray S. Non-nutritional rickets: Approach, precision medicine, and outcomes. World J Clin Pediatr 2026; 15(4): 122166 [DOI: 10.5409/wjcp.122166]
Corresponding Author of This Article
Sayantan Ray, MD, DM, Assistant Professor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences (AIIMS), Sijua, Patrapada, Bhubaneswar 751019, Odisha, India. sayantan.ray30@gmail.com
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Endocrinology & Metabolism
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Pathak PP, Ray S. Non-nutritional rickets: Approach, precision medicine, and outcomes. World J Clin Pediatr 2026; 15(4): 122166 [DOI: 10.5409/wjcp.122166]
World J Clin Pediatr. Dec 9, 2026; 15(4): 122166 Published online Dec 9, 2026. doi: 10.5409/wjcp.122166
Non-nutritional rickets: Approach, precision medicine, and outcomes
Pratyush Prateek Pathak, Sayantan Ray
Pratyush Prateek Pathak, Sayantan Ray, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Bhubaneswar 751019, Odisha, India
Author contributions: Pathak PP conceptualized the work; Pathak PP and Ray S performed a literature search, supervised the writing, provided intellectual input, and critically revised the manuscript. All authors have read and approved the final manuscript.
AI contribution statement: AI tools were not used during manuscript preparation.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Sayantan Ray, MD, DM, Assistant Professor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences (AIIMS), Sijua, Patrapada, Bhubaneswar 751019, Odisha, India. sayantan.ray30@gmail.com
Received: April 13, 2026 Revised: May 18, 2026 Accepted: June 4, 2026 Published online: December 9, 2026 Processing time: 160 Days and 23 Hours
Abstract
Rickets are chronic bone disorders marked by impaired mineralization of the growing skeleton. While most cases arise from nutritional deficiencies, non-nutritional forms are frequently underrecognized. Subtle signs such as alopecia in vitamin D dependent rickets type 2A, cataract in Lowe syndrome, dental abscesses or sensorineural hearing loss in X-linked hypophosphatemia can prompt timely diagnosis and referral. A structured approach combining growth and skeletal assessment, targeted biochemistry (calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D), radiography, and early genetic testing once nutritional deficiency or renal failure are excluded improves diagnostic accuracy. Molecular confirmation enables precise subclassification into hypophosphatemic and calciopenic rickets, supporting genotype-directed therapy, including burosumab for X-linked hypophosphatemia. Early, tailored treatment enhances radiographic healing, growth, and function. Emerging genotype-phenotype correlations further inform genetic counselling and prognosis, strengthening the multidisciplinary management of these complex disorders.
Core Tip: Non-nutritional rickets represent a heterogeneous group of disorders. Presentation before 6 months or after 2 years of age, stigmata of specific systemic illnesses, and lack of response to oral calcium and vitamin D should raise clinical suspicion. A systematic diagnostic algorithm can guide evaluation. Parathyroid hormone may serve as a useful initial biochemical discriminator between calciopenic and hypophosphatemic rickets. Fibroblast growth factor 23 assays help distinguish fibroblast growth factor 23-dependent and independent hypophosphatemic rickets subtypes. Levels of 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D help sub-classify heritable forms of calciopenic rickets. Several entities require molecular techniques for diagnostic confirmation, enabling precision medicine and genetic counselling.
