An 18-month-old boy with growth failure and gross motor skill regression

An 18 month-old boy was referred for evaluation of growth failure and regression in his motor skills. Before 12 months of age, he began pulling to stand and cruising but was no longer doing these skills at the time of assessment. His development was otherwise normal. Birth history and past medical history were unremarkable. There were no other concerns identified on review of systems or dietary history. Examination revealed a well-looking boy who was small, but did not have muscle wasting. He was alert and interactive. His growth parameters are shown in Figure 1. He sat unsupported, but did not bear weight or cruise. The remainder of his exam was normal. He was admitted to the Paediatric Medical Unit for ongoing investigation and management. (A) The patient’s weight and length on the WHO Growth Chart. (B) The patient’s head circumference and weight for length on the WHO Growth Chart. Investigations revealed a normal CBC and normal serum sodium, potassium, urea and creatinine levels. He had a negative celiac screen and normal sweat test. Extended electrolytes showed a normal calcium level at 2.3 mmol/L and a very low phosphate level at 0.67 mmol/L (normal range 1.5–2.2 mmol/L). Further investigations revealed the diagnosis. Further, bloodwork showed a mild metabolic acidosis, with pH 7.29, normal bicarbonate and base excess of −7.7 mmol/L. Urine studies showed a basic urine pH of >9, hyperphosphaturia and generalized aminoaciduria. He did not have glucosuria. His alkaline phosphatase was markedly elevated at 2777 U/L (normal range 145–320 U/L). A skeletal survey showed diffuse generalized osteopenia, cortical thinning, a rachitic rosary and multiple healing fractures of his extremities (Figure 2) and subtle widening of the metaphysis at the wrist. (A) Chest x-ray showing prominent costochondral joints, in keeping with a rachitic rosary. (B) Lower leg x-ray showing a healing fracture of the fibula, osteopenia and cupping and fraying of the distal bony metaphysis. The patient was transferred to the Nephrology team with a diagnosis of Fanconi syndrome causing hypophosphatemia and rickets. He was treated with Vitamin D and phosphorus supplementation and nutritional support. The underlying cause of his Fanconi syndrome is still to be determined. Rickets is a disorder characterized by impaired mineralization at the growth plate and thus is a disease that only affects growing children (1). It is caused by low serum levels of calcium (calcipenic rickets) or phosphorus (phosphopenic rickets). While calcipenic rickets is most often caused by Vitamin D deficiency, phosphopenic rickets is usually secondary to renal wasting of phosphorus. These renal causes include rental tubular acidosis (including Fanconi syndrome), X-linked or autosomal dominant hypophosphatemic rickets or Dent disease (2). While chronic hypophosphatemia is often asymptomatic, in severe or acute cases it can present with fatigue, muscle weakness and neurological symptoms, such as altered mental status and seizures (3). Rickets classically presents with bony abnormalities and the location and type depends on the age and developmental abilities of the child. Infants who are not walking typically present with upper limb abnormalities, whereas the classic bowing of the legs is only observed in weight bearing children (2). Poor linear growth and delayed motor milestones are less recognized clinical features, but are often seen in young children with rickets (1). Physical exam findings can be subtle, as with our patient. The differential for gross motor delay or regression is broad. In our case, the patient’s regression was likely due to a combination of bony pain secondary to healing fractures as well as an abnormal musculoskeletal system. This should be considered in the differential diagnosis of isolated motor developmental delay or regression. The patient in our case was referred for failure to thrive, and while there is no standard uniform definition for this diagnosis, he met typical criteria, including having a weight below the third percentile for age and weight curve dropping two major percentile lines. The differential diagnosis of a child with failure to thrive is often conceptualized as a) inadequate nutritional intake, b) increased output/malabsorption or c) increased metabolic demands (4). While this approach is useful, clinicians may think of ‘increased output’ as primarily gastrointestinal in origin instead of considering renal losses of phosphate, bicarbonate, amino acids and glucose, which may present with more subtle symptoms. In our case, the patient had poor linear growth, while his weight-for-length percentile was not as severely affected. His growth failure was presumably due to deficient mineralization at the growth plates and renal phosphate wasting. In our case, testing urea and creatinine levels alone did not elucidate any renal abnormality. It was only on evaluation of the blood gas, extended electrolytes and urine studies that the diagnosis was elucidated. Hyperphosphaturia and generalized aminoaciduria are detected with specific testing, whereas glucosuria can be seen on a routine urinalysis when present. Normoglycemic glucosuria occurs in many forms of renal Fanconi syndrome. However, in younger children, glucosuria is usually only seen with acute illnesses and tubular stress events. Therefore, the absence of glucosuria does not exclude a diagnosis of Fanconi syndrome in younger children, but can certainly aid in diagnosis when present. The differential for gross motor delay presenting as an inability to weight bear should include chronic musculoskeletal deformities and pain. Renal disorders cannot be excluded by testing urea and creatinine alone. Many renal disorders require additional tests including blood gas, extended electrolytes and urinalysis. These are abnormal in renal wasting diseases and can contribute to growth failure. We would like to acknowledge Dr Robyn McLaughlin and Dr Philip Acott for reviewing this manuscript.

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