Long-Term Follow-up of Hypophosphatemic Bone Disease Associated With Elemental Formula Use: Sustained Correction of Bone Disease After Formula Change or Phosphate Supplementation.

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus (R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution (R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children.

OBJECTIVE: Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. METHODS: A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. RESULTS: Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. CONCLUSION: The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.

Glycogen storage disease type III in Inuit children.

Glycogen storage disease type III (GSD III) was diagnosed in 4 Inuit children (3 confirmed, 1 suspected case) at our institution over the last decade. This rare autosomal recessive disease, which results from a deficiency of the debranching enzyme required for complete degradation of the glycogen molecule, has not been previously described in this population. The possible clinical presentations are heterogeneous, as is the spectrum of severity of this disease. The long-term sequelae can be severe, including recurrent hypoglycemia, hepatic cirrhosis and progressive muscle weakness. These 4 cases would suggest an increased prevalence of GSD III in the Inuit population. Therefore, it is important for health care providers caring for this population to consider and recognize this rare but serious disease.

Osteopenia and fractures in cystinotic children post renal transplantation.

Many of the end-organ effects of cystinosis are known to be risk factors for osteopenia; these include deposition of cystine crystals in bone, hypothyroidism, diabetes mellitus, primary hypogonadism, urinary phosphate wasting, and chronic renal failure. While transplantation may correct the latter, it exposes the child to other risk factors for diminished bone mass, notably the use of high-dose glucocorticoids. Our objective was to determine if these multiple risk factors translate into an increased occurrence of osteopenia, as measured by dual-energy X-ray absorptiometry (DEXA), and/or fractures in this population. We examined the charts, X-rays, and bone mineral density (BMD) of all cystinotic patients post renal transplant for whom this information was available. Lumbar spine BMD was measured by DEXA scan (Hologic 4500). Z-scores were corrected for growth parameters using previously published reference data. Fracture history and pertinent serum markers of bone metabolism were also analyzed. Of the 63 renal transplants performed at our institution, 11 children were transplanted due to cystinosis. Nine of these patients, 5 male and 4 female, had had BMD evaluations, with an average age of 14.3 years (range 5-17 years) at the time of initial BMD post transplant. The mean interval between transplant and BMD evaluation was 39 months (range 3-90 months). Surprisingly, 7 of 9 patients had normal uncorrected BMD values (z-scores -1.92 to +0.02) and 7 of 9 patients had normal corrected values (z-scores -1.20 to +1.93). Three patients suffered from a total of eight fractures. Of the 3 fracture patients, 2 had normal BMD. All patients maintained good graft function and had normal calcium/phosphate mineral status. Of note, 3 of 5 male patients had evidence of primary testicular failure at earlier ages than often described, and this may be an unrecognized risk factor for bone disease in this population. Despite the numerous risk factors for developing osteopenia, these results suggest that the majority of cystinotic patients post renal transplant do not experience reduced bone mineral content as measured by DEXA. However, the significant fracture history among these patients demonstrates that DEXA cannot be used to assess fracture risk in patients with nephropathic cystinosis.