Hypophosphatemia and Metabolic Bone Disease Associated With the Use of Elemental Formula: Case Report and Review

A small percentage of infants and children develop cow’s milk protein allergy which is usually treated with exclusive breastfeeding or extensively hydrolyzed formulas. Some children might still be reactive to hydrolyzed formulas and would need elemental amino acid-based formulas. Elemental formulas are also frequently employed in treating very low birth weight babies with significant intolerance to regular preterm formulas and the resulting poor growth. All pediatric formulas are usually prepared as per international guidelines to fulfill the macro- and micronutrient requirements of growing children across a wide range of volume intakes. However, an interesting correlation is being reported recently, between the use of a specific elemental formula and the development of hypophosphatemia and significant metabolic bone disease. We discuss this phenomenon by exploring the available evidence and report 2 similar cases that we managed in our practice.

Quantification of Isomer-Resolved Iodide CIMS Sensitivity and Uncertainty Using a Voltage Scanning Approach

Chemical ionization mass spectrometry (CIMS) using iodide as a reagent ion has been widely used to classify organic compounds in the atmosphere by their elemental formula. Unfortunately, calibration of these instruments is challenging due to a lack of commercially available standards for many compounds, which has led to the development of methods for estimating CIMS sensitivity. By coupling a Thermal desorption Aerosol Gas chromatograph (TAG) simultaneously to a flame ionization detector (FID) and an iodide CIMS, we use the individual particle-phase analytes, quantified by the FID, to examine the sensitivity of the CIMS and its variability between isomers of the same elemental formula. Iodide CIMS sensitivities of isomers within a formula are found to generally vary by one order of magnitude with a maximum deviation of two orders of magnitude. Furthermore, we compare directly measured sensitivity to a method of estimating sensitivity based on declustering voltage (i.e., “voltage scanning”). This approach is found to carry high uncertainties for individual analytes (half to one order of magnitude), but represents a central tendency that can be used to estimate the sum of analytes with reasonable error (~30 % differences between predicted and measured moles). Finally, GC retention time, which is associated with vapor pressure and chemical functionality of an analyte, is found to qualitatively correlate with iodide CIMS sensitivity, but the relationship is not close enough to be quantitatively useful and could be explored further in the future as a potential calibration approach.

Amino Acid Formulas in Patients with Gastrointestinal Diseases

Modern approaches for the management of children with gastrointestinal pathologies include optimal nutritional support that makes it possible to replete energy failure and restore essential nutrients balance. The article presents key information on gastrointestinal diseases in which modern amino acid formulas can be used to regulate nutritional status. The authors have conducted the extensive analysis of all available for now evidence on the efficacy, safety and utility of using such innovative medical technology as special elemental formula in gastrointestinal tract pathological conditions. This material is the basis for guidlines on the use of amino acid formulas developed by expert specialists of the Union of Pediatricians of Russia in 2020.

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.

SAT-076 Hypophosphatemic Rickets Secondary to Elemental Formula Use - Report on Two Cases

Background: Hypophosphatemic rickets (HR) is usually an inherited disorder, but it may also occur in several clinical settings as an acquired condition due to phosphate absorption and internal distribution issues. Recently it was described the association between the use of the elemental amino-acid based formula (AAF) and HR. Herein we report two male twins presenting this condition. Clinical case: Two monozygotic preterm (28 weeks + 5 days) brothers, born with extremely low birth weight (895 and 995 grams, -1,4 SDS and -0.9 SDS, respectively), received total parental nutrition from the 1st to the 7th day of life. Afterwards they started oral diet with milk and human milk fortifier FM85 for preventing metabolic bone disease of prematurity. After some weeks they developed abdominal distension, vomiting and hematochezia. Allergy to cow milk protein was suspected and the infants started receiving extensively hydrolyzed milk formula. So, FM85 was suspended and they were put on tricalcium phosphate (12.9%) supplementation from the 4th week of life on. As the gastrointestinal symptoms persisted, the formula was exchanged for elemental formula Neocate at 2 months of age, with improvement of those symptoms. After the 5th week of life the patients developed hypophosphatemia (2.8 mg/dL, reference 4.8-7.4 mg/dL), hyperphosphatasemia (1,619 IU/L and 2,173 IU/L; reference 70-350 IU/L) and low urinary phosphate excretion, keeping normal calcium and PTH ser um levels. Radiographic skeletal inventory showed under mineralized bones with irregular metaphyseal margins, but no signs of fractures. Calcium and phosphate supplementation doses were increased in attempt to correct the metabolic disturbances, and calcitriol was also started. Nevertheless, hypophosphatemia, hyperphosphatasemia and hypophosphaturia persisted. At 4 months of age, Neocate was switched to Alfamino, still an AAF. After that, phosphate serum levels went up until normalization and alkaline phosphatase started to decrease. Calcium and phosphate supplementation were decreased to keep their serum levels at the normal range for age. The boys were then discharged from hospital when they were 4 months old (45 days of life of corrected age), but the family could not afford Alfamino, switching back to Neocate. After that their phosphate serum levels went below normal range again. Conclusion: To our knowledge, this is the first report on monozygotic twins presenting AAF Neocate-related HR. The underlying mechanisms of Neocate induced hypophosphatemia is still elusive, since its content of phosphate and calcium:phosphate ratio are similar to other AAFs. These cases reinforce the importance of evaluating phosphate metabolism in infants receiving AAF while the pathophysiology of this condition is not entirely understood.