Clinical_Rounds_in_Endocrinology_Volume_II_-_Pediatric_Endocrinology

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phosphate solubility product results in impaired mineralization and conse-

quently rickets–osteomalacia.

27. How to classify vitamin D-related rickets?

Rickets can be classified as vitamin D-deficient or vitamin D-dependent on the

basis of serum 25(OH)D levels and therapeutic response to calciferol (ergocal-

ciferol or cholecalciferol) and/ or calcitriol. Vitamin D deficiency is characterized

by low levels of 25(OH)D and excellent therapeutic response to calciferol.

Vitamin D-dependent rickets (VDDR) can be due to inherited deficiency of

1 α-hydroxylase enzyme (VDDR type 1) or inactivating mutations in vitamin D

receptor (VDDR type 2). The differences among various forms of vitamin

D-related rickets are summarized in the table given below.

Parameters

Vitamin D

deficiency VDDR type 1 VDDR type 2

Synonyms − Pseudo-vitamin

D-deficiency rickets

Hereditary vitamin

D-resistant rickets

Age of presentation 3–18 months Infancy Infancy

Mode of inheritance Sporadic Autosomal recessive Autosomal recessive

Pathophysiology Deficiency of

vitamin D

Deficiency of renal

1 α-hydroxylase

Defective vitamin D

receptor

Associated features Nil Nil Alopecia

Serum calcium Low/low normal Low Low

Serum phosphorus Low Low Low

ALP Elevated Elevated Elevated

iPTH Elevated Elevated Markedly elevated

25 (OH)D level Low High Normal

1,25 (OH) 2 D level Normal/high Very low Very high

Response to calciferol Excellent No response No response

Response to calcitriol Good Excellent Most children are

resistant to therapy

even with high dose

28. What is vitamin D-resistant rickets?

The term vitamin D-resistant rickets encompasses disorders associated with

rickets that are nonresponsive to therapy with optimal doses of calciferol. The

causes of vitamin D-resistant rickets include hypophosphatemic rickets/osteo-

malacia, chronic renal failure, and renal tubular acidosis. VDDR type 1 and

VDDR type 2 are also considered as vitamin D-resistant rickets. Presence of

vitamin D-resistant rickets should be suspected if there is failure of appearance

of line of provisional calcification after 3 months of optimal therapy (600,000 IU)

with vitamin D (Fig. 5.9).

5 Rickets–Osteomalacia