Paediatrics: Rickets

Rickets

A disorder of the growing skeleton due to inadequate mineralization of bone as it is laid down at the epiphyseal growth plates. There is a char-acteristic widening of the ends of long bones and characteristic radiology. Osteomalacia occurs when there is inadequate mineralization of mature bone. Both rickets and osteomalacia may be present at the same time.

Causes

Malnutrition and calcium deficiency are common causes worldwide. Vitamin D deficiency is rare in developed countries, although inadequate exposure to sunlight and exclusive breastfeeding of 6–12mths during infan-cy are well recognized causes.

Calcium deficiency 

Dietary; malabsorption.

Vitamin D

·  Vitamin D deficiency: dietary; malabsorption; lack of sunlight; iatrogenic (drug-induced, e.g. phenytoin therapy).

·  Defect in vitamin D metabolism: vitamin D-dependent rickets type I (1A-hydroxylase deficiency); liver disease; renal disease.

·  Defect in vitamin D action: vitamin D-dependent rickets type II.

Phosphate deficiency

·  Renal tubular phosphate loss (isolated): hypophosphataemic rickets:

·  X-linked;

·  autosomal recessive;

·  autosomal dominant.

·  Acquired hypophosphataemic rickets:

·  Fanconi syndrome;

·  renal tubular acidosis;

·  nephrotoxic drugs.

·  Reduced phosphate intake.

Clinical features

·  Growth delay or arrest.

·  Bone pain and fracture.

·  Muscle weakness.

·  Skeletal deformities:

·  swelling of wrists;

·  swelling of costochondral junctions (‘rickety rosary’);

·  bowing of the long bones;

·  frontal cranial bossing;

·  craniotabes (softening of skull).

Diagnosis

·  Laboratory (see Table 12.3):

·  plasma calcium/phosphate/alkaline phosphatase/PTH;

·  vitamin D metabolites (25-hydroxyvitamin-D3 (25 OHD)/1,25-dihydroxyvitamin-D3 (1,25 OHD)).

Radiological: X-ray of wrists (generalized osteopenia/widening, cupping and fraying of metaphyses).

There are three characteristic stages in disease progression:

·Stage 1: low plasma calcium/normal plasma phosphate.

·Stage 2: normal plasma calcium (restored due to compensatory hyperparathyroidism).

·Stage 3: low plasma calcium and phosphate—advanced bone disease.

Stages 1 and 2 are biochemically evident only. Stage 3 has clinical features.

Vitamin D-dependent rickets (VDDR) type I

Autosomal recessive condition. Due to a deficiency in renal 1A-hydroxylase, the enzyme responsible for the conversion of 25-hydroxyvitamin-D3 to 1, 25 dihydroxyvitamin-D3. The condition is due to mutations in the 1A-hydroxylase gene, P450c1A.

Patients usually present with evidence of severe clinical rickets within the first 24mths of life.

Treatment 

Requires replacement dose of 1, 25 dihydroxyvitamin-D3 (calcitriol).

Vitamin D-dependent rickets type II

Autosomal recessive condition. This disorder is due to mutations in the vitamin D receptor gene, leading to end-organ resistance to vitamin D. The condition is also referred to as vitamin D resistant rickets.

Clinical, laboratory, and radiological features are similar to those seen in vitamin D deficiency and VDDR type I. However, a striking feature observed in the majority of patients with VDDR-type II is sparse body hair development or total alopecia. This finding is usually present at birth or develops during the 1st year of life

Treatment 

with supraphysiological doses of 1, 25 dihydroxyvitamin-D3 (e.g. up to 60mcg/day of calcitriol) is often successful, although responses are highly variable.