Reducing Metabolic Bone Disease Burden in Intestinal Failure Children on Home Parenteral Nutrition.

Objective: To determine the prevalence of secondary hyperparathyroidism in a cohort of pediatric patients receiving home parenteral nutrition. Methods: For a service review, a population-based cohort of 37 pediatric intestinal failure patients receiving long-term parenteral nutrition that underwent serial biochemical monitoring during a study period of approximately 4 years were examined. Following the production of an algorithm, a follow-up audit was carried out (n = 33) after approximately 6 months. Results: Of the 37 patients examined in the initial service review, 22 (59%) were found to have an elevated parathyroid hormone (PTH) during the period of monitoring and 5 (14%) had a persistently elevated PTH. In the follow-up audit following the implementation of an algorithm, the number with elevated PTH reduced to 6 (18%) and no patients had persistently high levels. Conclusion: Elevated PTH is a common biochemical finding in pediatric intestinal failure patients receiving home parenteral nutrition and its presence should alert clinicians to the need to optimize nutritional parameters such as calcium to phosphate molar ratio and vitamin D status; failure to do so may increase the future burden of metabolic bone disease in such patients. We propose that an algorithm may help in this endeavor.

Assessing bone formation in patients with chronic kidney disease using procollagen type I N-terminal propeptide (PINP): The choice of assay makes a difference.

BACKGROUND: Measurement of procollagen type I N-terminal propeptide (PINP) concentration in serum reflects the rate of type I collagen synthesis and can therefore be used as a bone formation marker. There are two methods of PINP quantification; the first measures the trimeric propeptide (intact PINP) and the second measures both the trimeric and monomeric propeptides (total PINP). Trimeric PINP is excreted via hepatic endothelial cells, whereas monomeric PINP is cleared renally. Therefore, in renal failure, the total assay has a positive bias with respect to the intact assay, due to monomeric PINP accumulation. The aim of this study was to compare the performance of both assays across all stages of chronic kidney disease. METHODS: Serum was taken from male (n = 111) and female (n = 105) patients attending a metabolic bone clinic, and these were partitioned into stages of chronic kidney disease 1-5. Each serum sample was analysed using the Roche electrochemiluminescence immunoassay for total PINP and the Immunodiagnostic Systems chemiluminescence immunoassay for intact PINP. RESULTS: Passing-Bablok regression analysis comparing both methods showed that with advancing chronic kidney disease there was a proportional positive bias affecting the total assay when compared with the intact assay. This proportional positive bias was statistically significant for chronic kidney disease stages 3b, 4 and 5. CONCLUSIONS: Based on this method comparison study, usage of the total PINP assay should be avoided in chronic kidney disease stages 3b, 4 and 5 (eGFR ≤44 mL/min/1.73 m2) and instead an intact assay used as the total assay overestimates PINP concentrations due to monomeric PINP accumulation.

Three-year follow up of using combination therapy with fresh-frozen plasma and iron chelation in a patient with acaeruloplasminemia.

Acaeruloplasminemia is a rare autosomal recessive condition caused by inactivating mutations of the CP gene encoding caeruloplasmin (ferroxidase). Caeruloplasmin is a copper-containing plasma ferroxidase enzyme with a key role in facilitating cellular iron efflux. We describe a case of a patient with acaeruloplasminemia, confirmed by genetic analysis, treated with combination therapy of monthly fresh-frozen plasma (FFP) or Octaplas and iron chelation over a 3-year period. This 19-year-old male was diagnosed at the age of 14 after developing issues with social interaction at school prompting investigation. Prior to this, he had been well with a normal childhood. He was found to have an iron deficient picture with a paradoxically high ferritin, with low serum copper and undetectable caeruloplasmin. Genetic testing identified a homozygous splicing mutation, c.(1713 + delG);(c.1713 + delG), in intron 9 of the caeruloplasmin gene. Ferriscan showed a high liver iron concentration of 5.3 mg/g dry tissue (0.17-1.8). Brain and cardiac T2-weighted magnetic resonance (MR) imaging did not detect iron deposition of the brain or heart respectively. Treatment with monthly Octaplas infusion was commenced alongside deferasirox (540 mg o.d.) in an attempt to increase caeruloplasmin levels and reduce iron overload, respectively. After 3 years of treatment, there was biochemical improvement with a reduction in ferritin from 1084 (12-250) to 457 µg/L, ALT from 87 (<50) to 34 U/L together with improvement in his microcytic anaemia. No significant adverse events occurred. This case report adds further evidence of treatment efficacy and safety of combined FFP and iron chelation therapy in acaeruloplasminemia.

Identification of a novel loss-of-function PHEX mutation, Ala720Ser, in a sporadic case of adult-onset hypophosphatemic osteomalacia.

Adults presenting with sporadic hypophosphatemia and elevations in circulating fibroblast growth factor-23 (FGF23) concentrations are usually investigated for an acquired disorder of FGF23 excess such as tumor induced osteomalacia (TIO). However, in some cases the underlying tumor is not detected, and such patients may harbor other causes of FGF23 excess. Indeed, coding-region and 3'UTR mutations of phosphate-regulating neutral endopeptidase (PHEX), which encodes a cell-surface protein that regulates circulating FGF23 concentrations, can lead to alterations in phosphate homeostasis, which are not detected until adulthood. Here, we report an adult female who presented with hypophosphatemic osteomalacia and raised serum FGF23 concentrations. The patient and her parents, who were her only first-degree relatives, had no history of rickets. The patient was thus suspected of having TIO. However, no tumor had been identified following extensive localization studies. Mutational analysis of the PHEX coding-region and 3'UTR was undertaken, and this revealed the patient to be heterozygous for a novel germline PHEX mutation (c.2158G>T; p.Ala720Ser). In vitro studies involving the expression of WT and mutant PHEX proteins in HEK293 cells demonstrated the Ala720Ser mutation to impair trafficking of PHEX, with ~20% of the mutant protein being expressed at the cell surface, compared to ~80% cell surface expression for WT PHEX (p<0.05). Thus, our studies have identified a pathogenic PHEX mutation in a sporadic case of adult-onset hypophosphatemic osteomalacia, and these findings highlight a role for PHEX gene analysis in some cases of suspected TIO, particularly when no tumor has been identified.

A readability assessment of online stroke information.

BACKGROUND: Patients and carers increasingly access the Internet as a source of health information. Poor health literacy is extremely common and frequently limits patient's comprehension of health care information literature. We aimed to assess the readability of online consumer-orientated stroke information using 2 validated readability measures. METHODS: The 100 highest Google ranked consumer-oriented stroke Web pages were assessed for reading difficulty using the Flesch-Kincaid and Simple Measure of Gobbledygook (SMOG) formulae. RESULTS: None of the included Web pages complied with the current readability guidelines when readability was measured using the gold standard SMOG formula. Mean Flesch-Kincaid grade level was 10.4 (95% confidence interval [CI] 9.97-10.9) and mean SMOG grade 12.1 (95% CI 11.7-12.4). Over half of the Web pages were produced at graduate reading levels or above. Not-for-profit Web pages were significantly easier to read (P=.0006). The Flesch-Kincaid formula significantly underestimated reading difficulty, with a mean underestimation of 1.65 grades (95% CI 1.49-1.81), P<.0001. CONCLUSIONS: Most consumer-orientated stroke information Web sites require major text revision to comply with readability guidelines and to be comprehensible to the average patient. The Flesch-Kincaid formula significantly underestimates reading difficulty, and SMOG should be used as the measure of choice.