Introduction : Most common cause of rickets is vitamin D deficiency. Genetic mutations in the metabolism and function of Vitamin D is a rarer cause of rickets.
Case report : A16 month old male presented with bilateral clavicular swelling, constipation, generalised weakness and poor growth. He also had delay in motor milestones and was only able to sit with support. He was born in the UK to consanguineous parents of Asian origin.
Examination: Weight and height were on 2nd centile. He had frontal bossing, rachitic rosary, widened wrists and ankles, limited dentition. Investigations: Adjusted Calcium : 1.17 (2.22.6 mmol/l), Phosphate 1.3 (0.91.8 mmol/l), ALP 2027 (60425 U/l) and PTH 44.5 (1.958.49 pmol/l). Vitamin D 62.4 (50150 nmol/l). X-ray showed severe rickets. Subsequent investigation results: 1,25-dihydroxyvitamin D undetectable result consistent with 1a-hydroxylase deficiency. Genetic investigation showed mutation in the CYP27B1 confirming the diagnosis.
Management : Initially treated with calcium supplement and Alfacalcidol. Calcium was gradually weaned off. He remains on Alfacalcidol. Follow up after 9 months: Rickets has healed on X-ray. Calcium and PTH levels have normalised to 2.49 mmol/l and 5 pmol/l respectively.
Discussion: Vitamin D dependent rickets type 1, is an autosomal recessive disorder characterised by lack of 1-alpha hydroxylase enzyme. As a result, 25(OH)D cannot be converted to active form 1,25(OH)2D. It occurs as a result of mutations in the CYP27B1. Treatment is correction of initial hypocalcemia with Ca supplements and active form of Vitamin D e.g. Alfacalcidol.
Summary: Vitamin D dependent rickets presents similarly to nutritional rickets.
In nutritional rickets the measured vitamin D level is 25(OH) D is low, but in VDDR1 it is normal or high as the genetic defects affects the 2nd hydroxylation of vitamin D to active 1,25(OH)D.
Routinely laboratories measure the inactive form, 25(OH)D.
When there is a clinical picture of rickets, but the initial vitamin D result is normal, that is above 50 nmol/l, this excludes nutritional Rickets.
In this case, it was key to liaise with Biochemistry laboratory to analyse 1,25 (OH)D level. This then allowed clinicians to initiate appropriate treatment and initiate genetic investigation.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes