Transient Hyperphosphatasemia Research Articles

P-049A 生体肝移植後経過中に認めたbenign transient hyperphosphatasemiaの1例(肝・胆道4, 第44回日本小児外科学会学術集会)

P-049A 生体肝移植後経過中に認めたbenign transient hyperphosphatasemiaの1例(肝・胆道4, 第44回日本小児外科学会学術集会)

Transient hyperphosphatasemia: A case report

Transient hyperphosphatasemia (THP) is characterized by temporary elevation of serum alkaline phosphatase (AP). We report a case of a 26-month-old girl referred for slow growth and found to have THP as AP levels returned to normal without active treatment. THP is a benign condition in healthy children, which resolves spontaneously without any intervention. In the absence of signs and symptoms of any underlying liver, bone or gastrointestinal disease, isolated elevation of AP levels should alert the clinician to a diagnosis of THP to avoid expensive, extensive, and unnecessary investigations.

Abstract #808: Transient Hyperphosphatasemia (TH): Rare Cause of Isolated Elevated Alkaline Phosphatase in an Adult Post Renal Transplant Patient

Abstract #808: Transient Hyperphosphatasemia (TH): Rare Cause of Isolated Elevated Alkaline Phosphatase in an Adult Post Renal Transplant Patient

Transient hyperphosphatasemia after pediatric liver transplantation.

Transient hyperphosphatasemia (TH), the incidence of which in healthy children is 1.5-2.8%, is associated with a temporary elevation of serum alkaline phosphatase (ALP) without any other liver function test (LFT) abnormalities. Fast α2 band, detected on agarose gel electrophoresis, is known to be a highly sensitive phenomenon in TH. The aim of this study was to elucidate the characteristics of TH after liver transplantation (LT). Five TH patients (6.0%) out of 83 who underwent LT between October 1996 and October 2014, were included in this study. Patient background, duration of TH, peak ALP, time course of ALP and its isoenzyme in TH, other LFT, and imaging results were retrospectively investigated. Median patient age at the time of peak ALP during TH was 24 months (range, 16-98 months). Mean duration of TH was 111.0 ± 48.0 days. At 6887 IU/L, median ALP was elevated without any other LFT abnormalities. The first α2 band was detected in all patients, and the band disappeared at the same phase of ALP normalization. All of the patients improved without any treatment. The prevalence of TH was significantly higher in the patients after LT than in age-matched healthy children (P < 0.05). The detection of fast α2 band in the early phase allows for effective diagnosis of TH after LT, and 3-4 month follow up without treatment is feasible.

Hiperfosfatasemia transitória benigna da infância e infeção a campylobacter jejuni

Introduction: Benign Transient Hyperphosphatasemia (BTH) is characterised by transient elevation of serum alkaline phosphatase (ALP) in the absence of liver or bone disease. It has been associated to several entities, namely infections.Case report: We describe the case of a healthy two-year-old child with intermittent episodes of fever, abdominal pain, vomiting and soft stool since two months ago, with no relevant changes on physical examination. The exams revealed elevated ALP (2474 U/L), with normal liver function, calcium and phosphorus. The stool culture was positive for Campylobacter jejuni. Clinical condition was resolved after antibiotic therapy with azithromycin. Six months later serum ALP values were normal.Conclusion: The age of presentation, the absence of underlying disease and subsequent normalization of ALP allow the diagnosis of BTH. It isn´t possible, according to the available literature, to guarantee if the infection was the cause of BTH or if it was the reason to perform the analytical study.

Alkaline Phosphatase in Healthy Children: Reference Intervals and Prevalence of Elevated Levels

Background: Transient hyperphosphatasemia (TH) is an often unnoticed benign entity, primarily affecting children below 5 years of age. However, the prevalence among healthy children is unknown. We used data from a Swedish pediatric reference interval project to estimate the prevalence of high alkaline phosphatase (ALP) among healthy children and to calculate pediatric reference intervals. Methods: Blood was collected from 699 subjectively healthy children aged 6 months to 18 years. After exclusion of subjects with high ALP, age- and gender-specific reference intervals were calculated. Results: Six children had ALP levels >16.7 µkat/l (>1,000 U/l), including 4 females and 2 males aged 7-22 months. The prevalence in the age group from 6 months to 2 years was 6.2% (6/97). None of the older children had levels of ALP >16.7 µkat/l. The study did not include the follow-up of these apparently healthy children. Consequently, conditions others than TH explaining the elevated ALP could not be excluded. However, general chemistry analyses, such as liver enzymes, calcium, intact PTH and vitamin D, were essentially normal in these children. Conclusions: The prevalence of high ALP among subjectively healthy children was approximately 2.4% below 5 years of age and 6.2% below 2 years. Reference intervals vary with age and gender.

Benign transient hyperphosphatasemia associated with Epstein–Barr virus infection

Benign transient hyperphosphatasemia associated with <scp>E</scp>pstein–<scp>B</scp>arr virus infection

Normal Bone Turnover in Transient Hyperphosphatasemia

Transient hyperphosphatasemia of infancy and early childhood (THI) is characterized by a temporary isolated elevation of serum alkaline phosphatase activity (ALP), predominantly its bone or liver isoform, in either sick or healthy children under 5 years of age. Return to normal ALP levels usually occurs within four months. Spontaneous rise of ALP might concern the physician, especially when treating seriously ill children. However, THI is considered a benign biochemical disorder with no clinical consequences. Some existing reports support the hypothesis that THI is a result of increased bone turnover. We present evidence of normal bone turnover in two children with THI. In a one-year-old girl and a boy of the same age, high ALP levels (31 and 109 μkat/L, respectively) were accidentally detected. The children had no signs of metabolic bone disease or of liver disease. The high ALP levels returned to normal in two months, thus fulfilling the diagnosis of THI. In both patients, serum parathyroid hormone and bone turnover markers, serum CrossLaps, and serum osteocalcin were neither elevated, nor did these markers follow the ALP dynamics, thus reflecting normal bone turnover in THI. Children with THI should be spared from extensive investigations and unnecessary vitamin D treatment. Conflict of interest:None declared.

Isolated idiopathic transient hyperphosphatasemia in an adult patient after renal transplantation: a case report

Transient hyperphosphatasemia (TH) is characterized by the isolated elevation of serum alkaline phosphatase (ALP) in children. There is no evidence of liver or bone disease and the ALP levels return to normal within 4 months. Few adult cases have been reported. Here, we report the case of TH in a 54-year-old woman, who for 4 years after receiving a renal transplant, was regularly followed up at a renal outpatient clinic. Her underlying disease was chronic glomerulonephritis, for which she was taking immunosuppressive drugs (cyclosporine and mycophenolate mofetil). Routine laboratory analyses revealed that her ALP level had risen to 909 IU/l, which is a seven-fold increase relative to the upper normal limit (35 - 130 IU/l). The levels of intact parathyroid hormone; the tumor markers CEA, α-FP, CA 19-9, and CA 125; and other serum parameters were normal. The patient lacked symptoms, relevant clinical signs, and evidence of acute infection or acute chronic gastrointestinal disease. Lymph node enlargement and malignancy were not detected on a physical examination and ultrasonographic analysis of the abdomen, respectively. A bone scan showed no evidence of bone pathology. ALP isoenzyme analysis by electrophoresis showed patterns similar to those seen in TH of infancy and childhood. The ALP levels of the patient returned spontaneously to 126 IU/l 5 months after diagnosis. While isolated hyperphosphatasemia in renal transplantation patients may be a benign condition, we recommend that such cases be differentially diagnosed from other diseases that can trigger hyperphosphatasemia, including malignancy, infection, bone and liver diseases.

Su2069 Clinical Predictors of Esophageal and/or Gastric Varices Diagnosed by Endoscopy in Children With Portal Hypertension

Introduction: Marked transient elevations of alkaline phosphatase (ALP) are sometimes seen in children. This entity, otherwise called transient hyperphosphatasemia of childhood or Ulysses syndrome can lead to extensive testing without identification of a specific etiology. Delayed renal clearance with elevated macro enzymes or viral infections are possible etiological factors. While the exact physiology is unclear, it typically resolves over a period of weeks to months and no intervention is required. We report a cohort of pediatric liver transplant patients with isolated elevations of ALP without any other clinical or biochemical abnormalities. Methods: Medical records of patients who underwent orthotopic liver transplant (OLT) at Texas Children's Hospital between 2006 2011 were reviewed retrospectively. All patients with marked elevations of ALP (>690, normal range 145-320) were included. The diagnosis, age of transplant, date of alkaline phosphatase increase and the time taken to normalize or steadily decrease were obtained. In addition, aminotransferases, EBV titers, immunosuppressive regimen and use of steroids to account for possible causes of ALP elevation were recorded. Results: We identified 10 patients with isolated marked elevation of ALP without any other biochemical abnormality. The average value of ALP levels was 4360 and the mean time to normalize was 7 months. The mean age of occurrence was 36 months (median 22) and the timing of this phenomenon after liver transplant varied between 7-38 months. There were no changes in EBV titers or immunosuppressive regimens around the time of ALP increase. None had any documented fevers or a positive infectious workup during the time of the episode. The characteristics of the patients are shown in the table. Discussion: We identified Ulysses syndrome in 7% of 142 patients transplanted since 2006, but children under age three were affected more often. Patients post-OLT are closely monitored for postoperative complications like graft rejection, biliary complications or infection which requires frequent lab tests including liver panel and immunosuppressant drug levels. However, there are instances where we see isolated elevations of ALP without other abnormalities as in our patient group. No infectious etiology or changes in medications were identified in these patients. However, it is possible that patients might have had associated viral syndromes during the time of these episodes that could not be tested due to lack of a comprehensive viral panel. All of the episodes resolved without any interventions. Starzl et al had previously reported a similar phenomenon in the early liver transplant era that is still common in the tacrolimus era. It is essential for hepatologists to recognize this benign entity and thus avoid unnecessary and invasive testing. Table

Transient hyperphosphatasemia: Revisited diagnostic criteria based on the study of 533 cases

Transient hyperphosphatasemia: Revisited diagnostic criteria based on the study of 533 cases

Transient hyperphosphatasemia of infancy and childhood in a boy with idiopathic persistent hyperphosphatasemia

Transient hyperphosphatasemia of infancy and childhood in a boy with idiopathic persistent hyperphosphatasemia

Elevated Alkaline Phosphatase in Children: An Algorithm to Determine When a “Wait and See” Approach is Optimal

Due to the possibility of underlying hepatobiliaryor bone diseases, the diagnostic work up of a child with elevated alkaline phosphatase (AP) levels can be quite costly. In a significant proportion of these patients, elevated AP is benign, requiring no intervention: hence, known as transient hyperphosphatasemia (THP) of infants and children. A 27-month old previously healthy Caucasian female was found to have isolated elevation of AP four weeks after the initial symptoms of acute gastroenteritis. One month later, when seen in hepatobiliary clinic, signs and symptoms of gastrointestinal, hepatobiliary, or bone disease were absent and physical examination was normal. The diagnosis of THP was made, and, as anticipated, AP levels normalized after four months. Using this case as an example, we suggest an algorithm that can be utilized as a guide in a primary care setting to arrive at the diagnosis of THP and avoid further tests or referrals.

Benign transient hyperphosphatasemia in infants and children: a prospective cohort

A total of 20 children with benign transient hyperphosphatasemia were prospectively evaluated with no additional investigations recommended except repeat serologic evaluation in 2-3 months. The average age of our patients was 2.5 years (range: 1 year 2 months-5 years 10 months). The serum levels of alkaline phosphatase averaged 2383 IU/L (range: 1013-5700 IU/L). Levels returned to normal within several months. This condition should be recognized by the clinician in order not to put patients through lengthy, expensive and unnecessary investigations.

Transient hyperphosphatasemia in children revisited

Although transient hyperphosphatasemia (TH) has been well known for decades, its etiology and pathophysiology remain unclear. We aimed to study the clinical characteristics of children diagnosed with TH compared to older studies in order to expand our knowledge and understanding of this condition and to try and find a subgroup of children who are more prone to develop TH. We retrospectively studied 60 children diagnosed at Maccabi Health Services and Bnai Zion Medical Center, Haifa, Israel with TH between the years 2003-08. One hundred and twenty-two children matched by age, gender and presenting symptoms served as the control group. The patients were divided into four subgroups by their presenting symptoms: infectious disease 33%, failure to thrive 28%, diarrhea 15% and other 23%. The Hydragel 7 ISO-PAL and Hydragel 15 ISO-PAL kits were used for the identification and quantification of ALP isoenzymes in human serum. The ALP levels of the study group were 805-8619 U\L (mean 2311 U\L), without differences between the subgroups. The mean duration of TH was 12 weeks. ALP isoenzymes levels were measured in one-third of the patients, and showed that the bone isoenzyme was elevated in most. Forty-three (71%) subjects were diagnosed in the second half of the calendar year. We could not establish an etiological explanation for TH. We presume that it is a complex mechanism in which different stimuli led to upregulation of the enzyme.

Transient hyperphosphatasemia in pediatric renal transplant patients - Is there a need for concern and when?

TH of infancy and early childhood is characterized by transiently increased S-ALP, predominantly its bone or liver isoforms. There are neither signs of metabolic bone disease or hepatopathy corresponding to the increased S-ALP, nor a common underlying/triggering disease. TH may also occur in children post-renal Tx, which may raise significant concerns and anxiety. We describe four patients aged 2.8-7 yr in whom the TH occurred at 11-34 (median = 28) months after Tx and lasted from 40 to 105 (median = 63) days. No obvious cause/trigger of TH could be found; the clinical status and bone turnover were not altered. In cases of TH post-Tx, we recommend the evaluation of basic biochemical indices and wrist X-ray. If these results are normal, TH is most likely the diagnosis and the S-ALP can be monitored over the next three months without further testing. In patients with persisting TH for more than three months and/or in children with pre-existing or suspected metabolic bone disease, further evaluation may be indicated. In conclusion, TH is a benign disorder in patients post-Tx. Detailed investigation including bone biopsy is only indicated in patients with persisting TH.

Benign Transient Hyperphosphatasemia of Infancy. A Common Benign Scenario, a Big Concern for a Pediatrician

Benign transient hyperphosphatasemia of infancy (BTH) is a condition characterized by disproportionately high levels of serum alkaline phosphatase (SAP). We report 4 cases of healthy patients with an elevated SAP. The mean age of the patients was 33 (14-52) months, with three females and one male. All children had a normal physical exam and anthropometric measures. The maximum values of serum alkaline phosphatase recorded in the 4 patients were: 11900, 6500, 9700 and 7600 UI/L respectively, with the rest of the laboratory exams and diagnostic images being normal. The clinical course of all the patients was favourable and no patient presented signs of symptoms of illness. Blood was drawn on 6 occasions in patients 1 and 5 occasions in the rest. Benign transient hyperphosphatasemia of infancy was diagnosed. It is important to know the characteristics of this condition to order the necessary amount of complementary studies.

Prevalence of Transient Hyperphosphatasemia Among Healthy Infants and Toddlers

To describe the prevalence and clinical characteristics of transient hyperphosphatasemia (TH) in a cohort of healthy infants and toddlers. We performed a secondary data analysis of healthy infants and toddlers enrolled in a study examining the epidemiology of vitamin D deficiency. From 2005 to 2007, children aged 8 to 24 months were enrolled during well-child visits at an urban primary care pediatric clinic. At enrollment, we collected data regarding sociodemographic and clinical characteristics. We measured serum levels of alkaline phosphatase (AP), 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium, magnesium, and phosphorus. We placed participants into 1 of 3 categories on the basis of serum AP levels: normal (AP: 110-400 U/L), intermediate (AP: >400 to 1000 U/L), and TH (AP: >1000 U/L). We used Fisher's exact test and analysis of variance to evaluate differences in characteristics among the 3 groups. Nine (2.8%) of 316 children had an AP level of >1000 U/L (mean: 2165 U/L). Sixteen children (5.1%) had an intermediate serum AP level (mean: 544 U/L). Mean weight-for-age, length-for-age, and weight-for-length z scores were similar across all 3 AP groups. Compared with the 291 children without TH, children in the intermediate AP and TH groups had similar mean serum levels of 25-hydroxyvitamin D, PTH, calcium, magnesium, and phosphorus. TH seems to be a relatively common condition among healthy infants and toddlers. TH was not associated with anthropometric measures, vitamin D status, PTH, or serum minerals. Recognition of this benign condition is important to avoid unnecessary investigations.

Transient hyperphosphatasemia in pediatric renal transplant patients — Is there a need for concern?

Transient hyperphosphatasemia in pediatric renal transplant patients — Is there a need for concern?

Comparative study on two colonic bowel preparations for patients with chronic constipation

Objective. To determine the efficacy, tolerance, and safety of oral sodium phosphate compared with polyethylene glycol in patients with chronic constipation. Material and methods. From May 2007 to October 2007, 100 patients with chronic constipation were prospectively randomized into two groups for colonoscopy. Group A (n=49) received sodium phosphate before colonoscopy, while Group B (n=51) received polyethylene glycol. During the same period, another 50 patients in Group C with normal defecation function were enrolled and received the polyethylene glycol preparation. Patients with intestinal stenosis found by colonoscopy were excluded. The quality of preparation was assessed by the endoscopist, who was blinded to the types of bowel preparation. Laboratory examinations including hematocrit, serum phosphorous, serum calcium, blood urea nitrogen, and serum creatinine were carried out in Groups A and B before and after preparation. A questionnaire was used to assess adverse effects and patients’ tolerance to the bowel preparation. Results. Two patients in Group A with a diagnosis of malignant tumor detected by colonoscopy were excluded. The baseline parameters, including weight, age, gender, endoscopic diagnosis, or constipation status, were homogeneously distributed in the three groups. It was shown that the quality of preparation in Group B was poorer than that in Group C (p<0.05). Compared with Group B, Group A showed better quality of preparation, a smaller amount of intestinal air bubble, and a higher number of defecations after taking the medicine (p<0.05 for all). There were no significant differences in acceptance of the two preparations and the prevalence of adverse effects. Transient hyperphosphatasemia was noted in four patients in Group A, but neither clinical symptoms nor hypocalcemia was observed. Conclusions. Based on our preliminary study, in the preparation of patients with chronic constipation for colonoscopy, sodium phosphate is just as well tolerated and safe as a standard polyethylene glycol preparation and might provide a better quality of bowel preparation.