Q1: What abnormalities are demonstrated on the plain radiographs of the wrist?

Radiograph of the left wrist (fig 1) shows an air gun pellet in the soft tissues of the forearm but, in addition, there is widening of the distal radial growth plate and irregularity, lucency and cupping of the radial and ulnar metaphyses consistent with rickets. The carpal bone age is delayed, at approximately 4 years, but a radiograph of the left hand showed a dissociation between the carpal bone age and that of the remainder of the hand. This can occur due to intercurrent illness and, in isolation, is not indicative of globally delayed skeletal maturation. The differential diagnosis of the wrist radiograph includes rickets secondary to vitamin D deficiency, an abnormality of vitamin D metabolism, target cell abnormalities, including renal tubular disorders, or tumour-induced rickets, and metaphyseal chondrodysplasias (box 1).

Q2: What biochemical tests would aid the diagnosis?

Biochemical investigation is aimed at assessing the degree of renal impairment and characterising the nature of the renal abnormality. Serum analysis revealed mild renal impairment with a mild acidosis and consequent mild secondary hyperparathyroidism: urea 6.5 mmol/l (normal range 2.5–6.5 mmol/l), creatinine 112 mmol/l (30–80), bicarbonate 18 mmol/l (20–26), sodium 134 mmol/l (132–145), potassium 3.4 mmol/l (3.5–5.5), glucose 8.9 mmol/l (2.5–8.0). The serum parathyroid hormone was mildly raised with normal serum calcium and marginally low serum phosphate at 0.97 mmol/l (1.00–1.80). There was no serological evidence of copper deficiency or Wilson's disease which can give these radiological appearances and the latter can also result in a Fanconi syndrome.

Urine analysis revealed a severe tubular aminoaciduria with evidence of mild tubular acidosis (total serum bicarbonate 18 μmol/l with a urine pH of 7) but the biochemical and clinical features did not correspond to a particular proximal or distal tubular defect. The biochemical and radiological features did not correspond to renal tubular acidosis (RTA) type I, in which there is severe hypokalaemia, nephrocalcinosis and, most often, an acute presentation, nor with RTA type IV in which there is hyperkalaemia.1 2 The absence of Fanconi syndrome of glycosuria, aminoaciduria and hyperphosphaturia also excluded RTA type II. Examination of the eyes did not demonstrate tapetoretinal degeneration which, with the lack of a salt-losing nephropathy, excluded the autosomal recessive Senior Loken syndrome which is a major cause of end-stage renal failure in children, accounting for 10–20% of cases. The late presentation and clinical features excluded vitamin D-dependent and X-linked vitamin D-resistant rickets, Lignac-Fanconi syndrome (cystinosis), and oxalosis.

Q3: What additional radiological investigation should be performed and what abnormalities might be expected?

In rickets secondary to renal causes, ultrasound and dimercaptylsuccinic acid (DMSA) scan may show features suggestive of a cause of renal failure, for example, small echogenic kidneys due to renal parenchymal disease, scarring, or reflux nephropathy. Nephrocalcinosis may be seen as part of RTA type I. In our patient, ultrasound showed that the kidneys were small for age (below the 5th centile), and mildly echogenic, with poor cortico/medullary differentiation but no definite evidence of nephrocalcinosis. The finding of a renal abnormality in conjunction with the results of serum and urine biochemistry excluded the diagnosis of rickets due to hepatic or nutritional disorders of vitamin D metabolism and also excluded primary metaphyseal chondrodysplasias.

A DMSA scan was performed to see if the cause of the small echogenic kidneys was reflux nephropathy. The scan showed almost no uptake of DMSA by the kidneys (fig 2). This can be due to inability to bind DMSA within the kidney or occasionally due to poorly functioning kidneys where the serum creatinine is over 300 mmol/l, ie, much higher than in this case. DMSA binds to plasma protein and, intracellularly, to cytosol proteins and mitochondria. Uptake occurs principally in the cells of the proximal tubules. Non-visualisation of the kidneys with DMSA is, therefore, an indication of the functioning state of the tubules. It was therefore concluded that these findings were indicative of mild chronic renal failure due to renal dysplasia in which there was a tubular defect leading to severe aminoaciduria and therefore, poor DMSA binding. It was not possible to exclude scarring on a DMSA scan with such poor DMSA uptake.

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Figure 2

DMSA scan of the kidneys.

Discussion

In chronic renal disease, metaphyseal abnormality results from failure of the kidneys to hydroxylate 25-hydroxy-vitamin D₃ and diminishing capacity to excrete phosphate. This stimulates production of parathyroid hormone, osteoclastic activity and bone resorption, resulting in temporary correction of serum calcium and phosphate.3 The serum calcium and phosphorus may be maintained within the normal range until the glomerular filtration rate goes below 25–30 ml/min when persistent hyperphosphataemia occurs. The growth plates, whilst appearing widened on plain radiographs, are actually narrowed when examined histologically with a region of osteitis fibrosa generalisata adjacent to the growth plate. This gives the widened growth plate appearance that simulates rickets. The growth plates are weak and susceptible to fracture resulting in a slipped epiphysis, although this is not usually seen until 11–16 years of age. Unlike renal osteodystrophy in adults, it is unusual in children to see phalangeal subperiosteal erosion and soft tissue and arterial calcification.

Management is aimed at reducing the degree of hyperparathyroidism, improving calorie intake and long-term monitoring of renal impairment. This case illustrates the importance of keeping an open mind when reporting trauma radiographs and a diagnostic pathway for evaluating metaphyseal abnormality.

Final diagnosis

Renal rickets secondary to non-specific renal protein-losing tubular abnormality.