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Published on: August 20, 2019
Genetic disorders and defects in vitamin d action
Peter J Malloy1, David Feldman
1Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford University, S-025 Endocrinology, Stanford, CA 94305-5103, USA. pjmalloy@stanford.edu
Summary
Two rare genetic disorders cause rickets in children due to defects in calcitriol synthesis or action. Understanding 1alpha-hydroxylase deficiency and vitamin D-receptor defects is key for diagnosis.
Area of Science:
- Pediatrics
- Genetics
- Endocrinology
Background:
- Rickets in children can stem from rare genetic conditions affecting vitamin D metabolism.
- Calcitriol, essential for calcium absorption, is synthesized via 25-hydroxyvitamin D-1alpha-hydroxylase.
- Defects in this enzyme or the vitamin D receptor (VDR) lead to distinct forms of rickets.
Purpose of the Study:
- To discuss and compare two rare genetic childhood diseases causing rickets.
- To differentiate between 1alpha-hydroxylase deficiency and hereditary vitamin D-resistant rickets.
Main Methods:
- Comparative analysis of two genetic disorders.
- Review of clinical presentations and underlying molecular defects.
Main Results:
- 1alpha-hydroxylase deficiency results from a defective enzyme, impairing calcitriol synthesis.
- Hereditary vitamin D-resistant rickets stems from a defective vitamin D receptor (VDR).
- Both conditions are autosomal recessive, presenting with hypocalcemia, secondary hyperparathyroidism, and severe early-onset rickets.
Conclusions:
- 1alpha-hydroxylase deficiency and vitamin D-dependent rickets type 2 share similar clinical features in infancy.
- Accurate diagnosis relies on distinguishing between enzyme deficiency and VDR defects.
- These rare genetic disorders highlight the critical roles of vitamin D metabolism and signaling in skeletal health.
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