Recurrent Bilateral Lower Motor Neuron Type of Facial Palsy with Hearing Impairment: Hyperphosphatemic Familial Tumoral Calcinosis

Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg2/mL2) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

A standard enteral formula versus an iso-caloric lower carbohydrate/high fat enteral formula in the hospital management of adolescent and young adults admitted with anorexia nervosa: a randomised controlled trial

Background The nutritional rehabilitation of malnourished patients hospitalised with anorexia nervosa is essential. The provision of adequate nutrition must occur, while simultaneously, minimising the risk of refeeding complications, such as electrolyte, metabolic, and organ dysfunction. The aim of this study was to compare the efficacy and safety of an iso-caloric lower carbohydrate/high fat enteral formula (28% carbohydrate, 56% fat) against a standard enteral formula (54% carbohydrate, 29% fat). Methods Patients (aged 15–25 years) hospitalised with anorexia nervosa were recruited into this double blinded randomised controlled trial. An interim analysis was completed at midpoint, when 24 participants, mean age 17.5 years (± 1.1), had been randomly allocated to lower carbohydrate/high fat (n = 14) or standard (n = 10) feeds. Results At baseline, there was no significant difference in degree of malnutrition, medical instability, history of purging or serum phosphate levels between the two treatment arms. A significantly lower rate of hypophosphatemia developed in patients who received the lower carbohydrate/high fat formula compared to standard formula (5/14 vs 9/10, p = 0.013). The serum phosphate level decreased in both feeds, however it decreased to a larger extent in the standard feed compared to the lower carbohydrate/high fat feed (standard feed 1.11 ± 0.13 mmol/L at baseline vs 0.88 ± 0.12 mmol/L at week 1; lower carbohydrate/high fat feed 1.18 ± 0.19 mmol/L at baseline vs 1.06 ± 0.15 mmol/L at week 1). Overall, serum phosphate levels were significantly higher in the lower carbohydrate/high fat feed compared with standard feed treatment arm at Week 1 (1.06 ± 0.15 mmol/L vs 0.88 ± 0.12 mmol/L, p < 0.001). There was no significant difference in weight gain, number of days to reach medical stability, incidence of hypoglycaemia, or hospital length of stay. Conclusions The results of this study indicate that enteral nutrition provided to hospitalised malnourished young people with anorexia nervosa using a lower carbohydrate/high fat formula (28% carbohydrate, 56% fat) seems to provide protection from hypophosphatemia in the first week compared to when using a standard enteral formula. Further research may be required to confirm this finding in other malnourished populations. Trial Registration: ANZCTR, ACTRN12617000342314. Registered 3 March 2017, http://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000342314

Association Between Admission Serum Phosphate and Risk of Acute Kidney Injury in Critically Ill Patients with Rhabdomyolysis: A Retrospective Study Based on MIMIC-III

Background The incidence of acute kidney injury(AKI) is high in critically ill patients with rhabdomyolysis. Limited evidence was proved of the association between serum phosphate levels at intensive care unit(ICU) admission and the subsequent risk of AKI. Our study aims to assess if serum phosphate level at admission was independently associated with AKI risk in these patients. Methods This study extracted and analyzed data from Medical Information Mart for Intensive Care-Ⅲ(MIMIC-Ⅲ,version1.4). Rhabdomyolysis was defined as a peak creatine kinase(CK) level higher than 1000 U/L. Serum phosphate was measured within the first day into the ICU and was categorized to 4 groups(<2.6, 2.6-3.4, 3.5-4.5, >4.5mg/dl). AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. Adjusted smoothing spline plots and multivariate logistic regressions were carried out to explode the association between serum phosphate and risk of AKI. Subgroup analyse was applied to verify the consistency of the association.Results Three hundred and twenty-one patients(67.8% male) diagnosed as rhabdomyolysis were eligible for this analysis. AKI occurred in 204(63.6%) patients of total. Incidence of AKI with admission serum phosphate groups<2.6, 2.6-3.4, 3.5-4.5 and>4.5mg/dl were 52.6%, 56.8%, 68.4% and 75.9%, respectively. Smoothing spline curve showed that there was a positive curve between the elevated phosphate values and increasing risk of AKI, and there was no threshold saturation effect. In multivariate logistic regression, OR was 1.3(95%CI 1.1-1.6, P=0.012, P trend=0.034) after adjusting confounders. Subgroup analyses proved the consistency of the relationship in these patients except in the strata of creatine kinase.Conclusion In rhabdomyolysis patients admitted to ICU, serum phosphate level at admission was independently associated with an increased risk of AKI. As phosphate levels rise, the risk of AKI increased.

Klotho overexpression protects against renal aging along with suppressions of transforming growth factor-β1 signaling pathways

Klotho is an anti-aging protein reported to suppress transforming growth factor (TGF)-b1 signaling. Aging kidneys are characterized by interstitial fibrosis, accumulation of cell cycle-arrested cells, and increased levels of oxidative stress. TGF-b1 signaling is involved in these processes. In this study, we investigated whether klotho overexpression improves these features in the kidneys of aging mice, and examined the inhibitory effect of klotho on signaling molecules related to transforming growth of TGF-b1. Klotho transgenic (KLTG) and wild type (WT) mice were used, and 8-week-old and 24-month-old mice were defined as young and aging, respectively. We found that klotho expression was decreased in aging WT mice, but it was maintained in aging KLTG mice. Klotho overexpression improved the survival of 24-month-old mice. Although the serum calcium level was significantly lower in aging KLTG mice than in aging WT mice, the serum phosphate level did not differ between these mice. Klotho overexpression attenuated the increases in blood pressure, serum blood urea nitrogen level, and serum creatinine level in aging mice. Interstitial fibrosis, accumulation of cell cycle-arrested cells, and oxidative stress did not differ between young KLTG and WT mice, but they were significantly suppressed in aging KLTG mice compared with aging WT mice. Furthermore, the expression of TGF-b1-related signaling molecules was increased in aging WT mice, whereas it was inhibited in aging KLTG mice. These data suggest that klotho overexpression protects against kidney aging along with suppression of TGF-b1 signaling pathways.

An Unexplained Hyperphosphatemia in an Hispanic Woman , a Diagnosis Challenge

Introduction Hyperphosphatemia could be a finding in renal failure, tumor lysis syndrome, hypoparathyroidism, and ingestion of exogenous phosphate. We present the case of a woman with hyperphosphatemia in which we finally diagnosed multiple myeloma, serum phosphate level achieved normal range after chemotherapy started. Although hyperphosphatemia in multiple myeloma is a very rare finding, there are some reports. The proposed mechanisms include a large amount of paraproteins that interferes with phosphorus level determination showing a false increased level. When samples have been deproteinated before analysis, serum phosphorus level can decrease obtaining a true level. This case reminds clinicians the importance of seeking additional causes for abnormal phosphorus levels before starting treatments that could lead to hypophosphatemia. Case report An hispanic woman at the 7th decade of life that only suffered from controlled hypothyroidism, who assisted with complaints of axial pain mainly in thoracic and lumbar segments. She denied neurological and B symptoms. She had a CT scan performed and was referred to the hematology service.On clinical examination we didn't find any neurological signs, no megalies and no palpable nodes. The patient brought a CT spine scan showing thoracic images suggestive of mets with collapse of 50% in T12-L1 and a mass in S2.With these findings we decided to start intrahospitalary studies for excluding malignancy.Her relevant laboratories were: creatinine 0,7, BUN 25, Hemoglobin 9 gr/dl VCM 102 WBC 3330 Granulocytes 55% Platelet 222.000, UN 10,7, albumin 2.8, Lactate dehydrogenase 425. A series of labs seeking secondary causes of malignancy was made including plasmatic cell neoplasie.The hepatic function was normal but an unusually high Phosphorus level was detected (19,6) with normal calcemia (8.98), the tumoral biomarkers were in normal range (CEA, CA 19-9, Ca 125, AFP) and an elevated B2 microglobulin (8) was found. Additional labs included bence jones protein and PTH, both in normal range. A new Thoracic CT described mosaic infiltrates and an extensive bone involvement suggestive of lytic metastatic changes. The abdomen CT showed multiple lytic lesions in lumbo-sacral spine and pelvis, The skull radiography had lytic lesions too. The nephrology service was required by the Hyperphosphatemia and they asked about external intake of phosphorus finding that she was taking "hydrolyzed collagen", so they started iv fluid and chelators (aluminium hydroxide and no calcium chelators).Because of unresponsive hyperphosphatemia, nephrology started hemodialysis.Hematology found high IgG levels (5500) concluding the need for bone marrow studies . Finally a the bone marrow study was performed and prescribed steroids on suspicion of Multiple myeloma. Until this day the Phosphorus level still remained in high levels (17,7) despite hemodialysis sessions. The bone marrow study revealed a plasmatic cell population of 28,9% with big and abundant cytoplasm, some of them with binucleations suggestive of infiltration by plasmatic cell neoplasie. The seric electrophoresis revealed a paraprotein (seric protein of 9,3 with a monoclonal peak of gamma region of 3,4 gr/dl), the seric immunofixation was positive for a monoclonal IgG lambda component. With this report we began chemotherapy treatment for Myeloma with CyBorD regimen (Cyclophosphamide, Bortezomib, dexamethasone). After treatment was initiated, phosphorus level began to lower and achieved normal range (4.28) in the first two weeks. Then she was discharged to continue outpatient management. Nowadays she is receiving her 3rd chemotherapy cycle without complications, her phosphorus level still remains within normality. Conclusions Spurious hyperphosphatemia in patients with paraproteinemias like multiple myeloma can occur. The IgG monoclonal can interfere with the phosphomolybdate principle used in the assay of serum phosphate on most automated chemistry analysers. For labs which do not have a multilayered film technology based system, a serial dilution analysis of the suspected analyte could be performed. Disclosures No relevant conflicts of interest to declare.

Prevalence, progression and implications of breast artery calcification in patients with chronic kidney disease

Breast artery calcification (BAC) is increasingly recognized as a specific marker of medial calcification. The present retrospective observational cohort study aimed to define the prevalence, progression rate, risk factors and clinical implications of BAC in chronic kidney disease (CKD) patients across stages of disease. Presence and extent of BAC were determined on mammograms in 310 females (58.7 ± 10.8 yrs, Caucasian) with CKD across stages of disease (CKDG2-5D n = 132; transplant recipients [Tx]: n = 178). In a subset of 88 patients, a repeat mammography was performed, allowing to calculate the annualized BAC rate. Overall, BAC was observed in 34.7% of the patients. BAC prevalence (P = 0.02) and BAC score (P = 0.05) increased along the progression of CKD. In the overall cohort, patients with BAC were characterized by older age, more cardiovascular disease, more inflammation, higher pulse pressure, and borderline higher prevalence of diabetes, and were more often treated with a vitamin K antagonist. BAC progression rate was significantly lower in Tx as compared to CKD G5D. Progressors were characterized by more inflammation, worse kidney function, higher BAC score, higher serum phosphate level (Tx only) at baseline and were more often treated with a vitamin K antagonist. Major adverse cardiovascular event free survival was significantly worse in Tx with BAC. In conclusion, BAC is common among CKD patients, progresses at a slower pace in Tx as compared to CKD5D, and associates with dismal cardiovascular outcomes. BAC score, kidney function, serum phosphate at baseline and vitamin K antagonist usage seem to be important determinants of progression.

Phosphaturic mesenchymal tumors: radiological aspects and suggested imaging pathway

Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal neoplasms of soft tissue or bone origin that can give rise to a challenge in diagnostic imaging. These tumors are frequently associated with tumor-induced osteomalacia, also called oncogenic osteomalacia, which is a rare paraneoplastic syndrome characterized by ectopic secretion of fibroblast growth factor 23, a hormone that regulates serum phosphate level. PMTs show polymorphic features on both radiological findings and histological examination, causing problems in diagnosis owing to their similarity with other mesenchymal tumors. Thus, this paper aims to describe radiological aspects of PMTs and suggest an imaging pathway for accurate diagnosis throughout the evidence from the literature review.

Genotype and Phenotype Analysis in X-Linked Hypophosphatemia

Background: X-linked hypophosphatemia (XLH) is the most frequent form of hypophosphatemic rickets and is caused by mutations in the PHEX gene. We analyzed genotype-phenotype correlations in XLH patients with proven PHEX mutations.Methods:PHEX mutations were detected in 55 out of 81 patients who clinically presented with hypophosphatemic rickets. The patients were grouped into nontruncating (n = 9) and truncating (n = 46) mutation groups; their initial presentation as well as long-term clinical findings were evaluated according to these groups.Results: Initial findings, including presenting symptoms, onset age, height standard deviation scores (SDS), and laboratory tests, including serum phosphate level and tubular resorption of phosphate, were not significantly different between the two groups (onset age: nontruncating mutation group, 2.0 years, truncating mutation group, 2.2 years; height SDS: nontruncating mutation group, −1.9, truncating mutation group, −1.7; serum phosphate: nontruncating mutation group, 2.5 mg/dL, truncating mutation group, 2.6 mg/dL). However, at their last follow-up, the serum phosphate level was significantly lower in patients with truncating mutations (nontruncating mutation group: 3.2 mg/dl, truncating mutation group: 2.3 mg/dl; P = 0.006). Additionally, 62.5% of patients with truncating mutations developed nephrocalcinosis at their last follow-up, while none of the patients with nontruncating mutations developed nephrocalcinosis (P = 0.015). Orthopedic surgery due to bony deformations was performed significantly more often in patients with truncating mutations (52.3 vs. 10.0%, P = 0.019).Conclusion: Although considerable inconsistency exists regarding the correlation of truncating mutations and their disease phenotype in several other studies, we cautiously suggest that there would be genotype-phenotype correlation in some aspects of disease manifestation after long-term follow-up. This information can be used when consulting patients with confirmed XLH regarding their disease prognosis.