Benign Transient Hyperphosphatasemia Research Articles

Benign transient hyperphosphatasemia in the pediatric population: a single center cohort study.

Alkaline phosphatase (ALP) can be increased in a benign condition known as benign-transient hyperphosphatasemia (BTH). We aimed to evaluate the demographic, and clinical characteristics of infants and children with BTH. In our retrospective study, infants and children diagnosed with BTH between September 2019 and September 2023 were included. Of 249 children with elevated ALP levels, 95 (38.1 %) had BTH. The mean age at diagnosis of children with BTH was 2.4±1.3 years (min 0.6- max 6.2 years). ALP mean value was 2,587±1252 U/L (min 972- max 5757 U/L). ALP value was an average 7.4±3.6 times higher than the corresponding upper limit of normal. The second measurement was made after an average of 13.2±6days, and a statistically significant difference was detected compared to the first value, with a decrease of 61±23 % in the ALP value (p<0.001). ALP value returned to normal in an average of 44±29.2days. Elevated ALP was detected during infection in 49 (51.6 %) children. When the sample was divided into those under 2 years of age and aged 2 and over, no statistical difference was observed in ALP levels in the time it took for ALP levels to return to the normal range (p=0.480). BTH should be kept in mind if high serum ALP is detected in children without clinical or laboratory suspicion of bone or liver disease. In the follow up detecting a significant decrease trend compared to the first value may be guiding for BTH.

Retrospective evaluation of cases of benign transient hyperphosphatasemia

This study aimed to evaluate the demographic, clinical, and laboratory characteristics of children with benign transient hyperphosphatasemia (BTH) and to increase awareness of BTH. Children with BTH followed up in a tertiary pediatric endocrinology outpatient clinic were included in this retrospective study. Children who were aged under 5 years, who had no evidence of liver, kidney, or bone disease, who had serum total alkaline phosphatase (ALP) levels above 1000 IU/L, and whose ALP values resolved within 4 months, were included in the study. The study included 10 infants and children (4 females) with BTH who were referred to our clinic during 1 year for high ALP levels. The mean age was 2.4±0.5 years. The mean weight SDS was -0.24±1.27 and the mean height SDS was -0.51±0.67. The mean ALP level was 2.395±934 IU/L. The mean normalization time for serum ALP was 2.4±1.1 months. Benign transient hyperphosphatasemia is an entity that occurs in healthy infants and children without evidence of liver or bone disease and resolves without intervention.

Benign transient hyperphosphatasemia in infants and children: a retrospective database study.

Benign transient hyperphosphatasemia seems to be a disorder described among otherwise healthy infants and children, which resolves spontaneously. Other known causes of markedly elevated serum ALP should be excluded, especially bone and liver disease. Higher awareness and recognition of this benign condition are important in order to avoid unnecessary tests and parental anxiety. • Benign transient hyperphosphatasemia is a benign condition characterized by greatly increased serum alkaline phosphatase without laboratory or clinical evidence of underlying bone or liver disease, which usually resolves spontaneously, with no intervention. • In the case of an incidental finding of high serum alkaline phosphatase in an otherwise healthy infant or child with no other clinical or laboratory suspicion of bone or liver disease, we recommend repeating the alkaline phosphatase level within a few months in order to confirm the resolution of this condition. • When benign transient hyperphosphatasemia is suspected, a "wait and see" approach is optimal in order to avoid unnecessary investigations and parental anxiety.

ДОБРОКАЧЕСТВЕННАЯ ТРАНЗИТОРНАЯ ГИПЕРФОСФАТАЗЕМИЯ У ДЕТЕЙ: 12 НОВЫХ СЛУЧАЕВ И ОБЗОР ЛИТЕРАТУРЫ

Benign transient hyperphosphatasemia of childhood (TH, BTH, BTHC) is a condition characterized by a temporary significant increase in the level of alkaline phosphatase in healthy people. This condition is transient and it does resolve without treatment within 2 to 4 months, does not have any long-term consequences (according to the analysis of the bibliographical sources and the Authors’ own observations). BTH is most often detected in children under the age of 5 y/o with the peak under 2 years, however there are sporadic cases in adults observed. In addition, there are descriptions of familial cases of TH that are clinically identical to the sporadic ones. Authors present twelve own observations of BTH cases and the bibliographical review on the topic. The criteria for BTH diagnosing are formed and a benign course of this condition had been confirmed.

Transient Hyperphosphatasemia in an Adolescent and an Adult Renal Transplant Patient

In renal transplant patients receiving immunosuppression, a significant increase in alkaline phosphatase (ALP) might be indicative of liver or bone diseases caused by many factors. In infancy and early childhood, a transient and therefore benign increase in ALP often has been described, usually during a course of infectious disease. Rarely, transient hyperphosphatasemia occurs in adults. We herein present 2 cases of transient hyperphosphatasemia in an adolescent and an adult renal transplant recipient, respectively. In the first case, a 17-year-old adolescent presented with an ALP value up to 2451 U/L, reporting no symptoms. In the second case, a 56-year-old woman with a second well-functioning kidney transplant presented with an ALP value up to 1532 U/L, without symptoms. In both cases, the biochemical profile and ultrasound study were negative for liver disease while no viral or other type of infection was detected. Bone scanning was within normal range and parathyroid hormone was also normal. However, bone ALP was measured at 8.9 and 11.9 times, respectively, above reference values. ALP electrophoresis had a characteristic pattern with involvement of both liver and bone-specific isoforms. About 6 weeks after their peak, ALP values gradually returned to normal range. Benign transient hyperphosphatasemia, although rare, should be considered in the differential diagnosis of isolated ALP increase, even in adult patients with kidney transplant. Electrophoresis of ALP could narrow the diagnostic procedure in cases when neither liver nor bone disease is clinically apparent.

Benign transient hyperphosphatasemia - a cause for alarm or a benign condition

Benign transient hyperphosphatasemia (BTH) is a condition which occurs in children younger than five years, characterized by a complete absence of specific clinical and laboratory findings of bone or liver diseases and a five or even 20–70-fold increase in serum of alkaline phosphatase levels(ALP). The aim of this case report was to point out that elevated levels of ALP are not always related to serious bone and liver diseases. We described three healthy patients, which were referred to our out-patient clinic by their primary care physicians because of markedly elevated levels of ALP. The diagnosis of BTH was based on a thorough physical exam, a wide range of laboratory and imaging tests, which excluded liver or bone disease as a cause for elevated ALP. BTH is not very well-known and managed in daily clinical practice. Primary care physicians should consider this diagnosis in cases with elevated ALP in otherwise healthy infants and toddlers, refrain from unnecessary tests, prescribing higher doses of vitamin D3 or referral to tertiary level pediatric institutions.

Benign transient hyperphosphatasemia in children

Introduction/Objective. Benign transient hyperphosphatasemia (BTH) is a pathogenetic insufficiently clear clinical entity that is mostly seen in infants and young children. The objective of this paper is to present our experience regarding the age of occurrence, the conditions of the discovery, and the length of duration of BTH in children. Methods. The study was realized on a sample of 18 children, nine boys and nine girls, aged 10?42 (21.06 ? 9.35) months with BTH. The diagnosis of BTH is based on the absence of bone and hepatobiliary diseases, and its spontaneous disappearance over the course of several months. Results. One patient was in the first year, 13 in the second, three in the third, and one in the fourth. Isolated high activity of serum alkaline phosphatase, which was 2.04?21.9 (8.05 ? 5.31) times above the upper reference value for the corresponding age, in 14 cases it was found during the acute diarrhea, and in four with acute rhinopharyngitis, of which in two complicated with otitis media. The cause of diarrhea in six cases was rotavirus, in two Campylobacter, and in one adenovirus, and otitis media in one case was caused by Streptococcus pneumoniae, while in others, etiologic factors of infection were not identified. Spontaneous normalization of serum alkaline phosphatase activity was recorded between one and three months after the onset. Conclusion. BTH is a harmless biochemical disorder that spontaneously subsides within three months after initial observation. It is found randomly as a routine laboratory finding most often within the treatment of acute gastrointestinal and respiratory infections.

A case series of benign transient hyperphosphatasemia from a pediatric endocrinology reference health facility in Turkey.

IntroductionBenign transient hyperphosphatasemia (BTH), even a known condition, is not very well managed by primary care physicians. The diagnostic criteria for BTH were alkaline phosphatase (ALP) levels above 3-5 times greater than the age adjusted upper limit of normal among children under 5 years with no evidence of liver or bone disease whose ALP values resolved within 4 months.MethodsThis study involved 15 patients aged 0-5 years, who were referred to the pediatric endocrinology clinic for elevated ALP levels. They were diagnosed with BTH. We examined demographic and biochemical parameters including ALP and ALP isoenzymes, liver enzymes, calcium, phosphate, and parathormone (PTH) levels to rule out liver or bone disease as a cause for hyperphosphatasaemia.ResultsOf 15 patients 7 were male and 8 were female. Mean age was 2.45 ± 1.09 (range 1.2-4.6) years. Mean serum ALP level was 2315 ± 1028 IU/L (1102-4662), while liver enzymes, calcium, phosphate, PTH and vitamin D3 levels were in normal ranges. The mean normalization period of ALP was 2.4 ± 1.1 (0.5-4) months, and all were normal at the end of 4 months without any treatment.ConclusionThis study and literature knowledge related to BTH has shown that being aware of BTH is very important for a primary care physician. Paediatricians can conveniently manage the differential diagnosis and follow up this period of elevated ALP.

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)

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.

Benign transient hyperphosphatasemia associated with Epstein–Barr virus infection

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

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.

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.

Hiperfosfatasemia transitória benigna da infância

OBJETIVO: Relatar uma série de casos de hiperfosfatasemia transitória benigna da infância (HTBI). DESCRIÇÃO: São descritas quatro meninas. A faixa etária variou de 11-45 meses (mediana: 13 meses). Ao diagnóstico, a fosfatase alcalina sérica estava aumentada de 1,1-6,1 vezes (mediana: 1,36 vezes) o valor de referência. O retorno à normalidade ocorreu entre 7-11 meses (mediana: 9 meses). Não havia evidência de doenças ósseas, hepáticas, endócrinas, ou uso de medicamentos associados à elevação da fosfatase alcalina. Uma paciente apresentou infecções de vias aéreas superiores precedendo o diagnóstico da hiperfosfatasemia. Alanina aminotransferase, aspartato aminotransferase, cálcio, fósforo e magnésio estavam normais em todos. O paratormônio foi dosado em três crianças, estando normal em todas. Em dois pacientes, a investigação para hepatites A, B e C foi negativa. A fosfatase alcalina estava normal em três dos quatro pares de pais testados. COMENTÁRIOS: HTBI é uma patologia autolimitada, benigna e de resolução espontânea, que acomete crianças abaixo de cinco anos, sem evidência clínica ou laboratorial de doença óssea, hepática ou endócrina subjacente. A etiologia é desconhecida. Esta possibilidade deve ser considerada no diagnóstico diferencial da hiperfosfatesemia para evitar exames e procedimentos desnecessários.

Idiopathic Severe Elevation of Serum Alkaline Phosphatase Following Adult Renal Transplantation: Case Reports

Transient hyperphosphatasemia (TH) in infancy is a benign condition characterized by elevated alkaline phosphatase (ALP) levels severalfold the adult upper limits, occurring mainly in children under 5 years, without evidence of liver or bone disease, and a return to normal ALP levels by 4 months. Herein we have reported 3 cases of TH in adults following renal transplantation. The first case, a 47-year-old woman, blood group AB positive, had hypertensive renal disease. Five months after successful renal transplantation from a deceased donor she had a 50-fold increase in ALP. The second case, a 34-year-old man, blood group A positive, had renal failure due to IgA nephropathy. Nine weeks after a second renal transplant from a deceased donor a 25-fold increase in ALP was noted. The third case, a 45-year-old woman, blood group A positive, experienced renal failure 15 years earlier of unknown etiology. Thirteen years after her second renal transplant a 12-fold increase in ALP was observed during a routine follow-up. In all cases, the isolated ALP serum levels returned to normal limits within 12 weeks. Bone scans and abdominal ultrasounds during these periods were normal with no evidence of bone or liver disease. ALP isoenzyme electrophoresis revealed a pattern characteristic of TH of infancy and childhood. The 3 cases reported highlight the occurrence of benign TH in adults, with renal transplantation. However, liver disease, bone disease, and infection should be excluded first in these susceptible individuals on immunosuppression before establishing the diagnosis of TH.

Clinical Features and Natural Course of Benign Transient Hyperphosphatasemia in Children

목 적: 한국인 소아에서 양성 일과성 고인산분해효소 혈증(Benign transient hyperphosphatasemia, BTH)의 임상적 특징 및 자연 경과를 살펴보고자 하였다. 방 법: 2006년 6월부터 2007년 7월까지 분당서울대학교병원 소아과를 내원한 환아 중 Kraut 등의 진단기준에 따라 BTH로 진단된 17명의 의무기록과 검사결과를 후향적으로 분석하였다. 결 과: 총 17명의 환아 중 남아가 6명, 여아가 11명이었으며, 연령은 평균 26.9 ${\pm}$ 13.8개월(범위: 9~49개월)이었다. 동반된 질환으로는 감염성 질환이 52.9%로 가장 많았고, 계절적으로 9월에서 12월 사이에 더 높은 발생률을 보였다. 첫 내원 시 측정한 혈청 ALP는 평균 2500.2 ${\pm}$ 1165.1 U/L이었고, 모든 환아에서 7주 내에 혈청 ALP가 정상 또는 정상 상한치의 두 배 이내로 감소하였다. ALP isoenzyme 검사를 시행한 7명의 환아 중 3명에서 간 분획과 골 분획의 증가가 있었고, 4명은 골분획의 증가만을 보였다. 결 론: 한국인 소아에서 BTH의 임상적 특징 및 경과를 이해함으로써 ALP 상승 소견을 보이는 영유아에서 불필요한 진단적 검사들을 지양하며 임상 경과의 관찰을 통해 ALP 활성도의 정상화 여부를 확인하도록 하여야 한다. 【Purpose: This study was conducted to analyze the clinical manifestation and natural course of benign transient hyperphosphatasemia (BTH) in children. Methods: A total of 17 children diagnosed with BTH between June 2006 and July 2007, were included in this study. Clinical records and laboratory tests were analyzed retrospectively for all children. Results: The mean age of the patients was $26.9{\pm}13.8$ months (range: 9 to 49 months). Nine of the 17 BTH cases (52.9%) occurred in patients that had previously suffered from infectious diseases. While the patients were suffering from BTH, the mean serum level of alkaline phosphatase (ALP) was $2,500.2{\pm}1,165.1$ U/L, however, these elevated serum ALP levels normalized within 7 weeks of recovery in all cases. In addition, a seasonal peak in the onset of BTH was observed from September to December. Further, the measurement of ALP isoenzymes in 7 of the patients with BTH, revealed a marked elevation of bone fraction. Conclusion: It is important for pediatricians to understand the clinical manifestation and benign course of BTH to avoid unnecessary diagnostic evaluation in children showing a transient increase in ALP activities.】

Alkaline phosphatase isoenzymes in children with respiratory disease

Aim: To present the electrophoretic pattern of alkaline phosphatase (ALP) isoenzymes in serum of infants and children exhibiting increased total ALP catalytic activity in the course of acute respiratory disease. Subjects and methods: Results obtained in 21 children (17 of them infants), including 13 male and eight female children aged 2 months to 8 years, hospitalized for respiratory diseases are presented. Total ALP catalytic activity was determined and electrophoretic separation of ALP isoenzymes was performed in children's sera. Results: Increased total ALP catalytic activity (range, 528-5622 U/L) during hospital stay was recorded in eight (38.1%) children. A typical picture of be-nign transient hyperphosphatasemia (TH), which implies the occurrence of fast anodal fraction (faster than hepatic fraction) and near-cathode fraction (faster than bone fraction), was recorded in five children. The placental-like isoenzyme was detected in two children. Expression of bone fraction and placental-like fraction was recorded in a rachitic child. Prehepatic ALP was expressed in two children, and hepatic ALP isoenzyme in one child. Conclusion: Acute respiratory disease in infants and children may entail transient increase in the ALP catalytic activity with the occurrence of various isoenzyme bands such as fast anodal and near-cathode fraction (in TH), prehepatic fraction and placental-like fraction. TH is verified when total ALP activity has decreased and returned to reference intervals. In this case, no additional testing is required.

Hiperfosfatasemia transitória benigna na infância

&lt;span class="texto"&gt;A hiperfosfatasemia transitória benigna na infância (HTBI) é uma condição pouco conhecida, que se traduz por um estado benigno e de bom prognóstico. A HTBI resulta do aumento súbito e transitório na concentração sérica da fosfatase alcalina (FA) em crianças sadias. A sua etiopatogenia é ainda incerta, porém a diminuição do clearance da enzima na circulação tem sido considerada o mecanismo mais provável. Para divulgar os conhecimentos atuais acerca do diagnóstico da HTBI, foram selecionados, no Medline, os artigos de periódicos médicos internacionais mais relevantes desde a descrição inicial desta condição, em 1954. Os critérios para diagnóstico de HTBI são: acometer crianças com idade inferior a cinco anos, ausência de sintomas ou presença de sintomas associados a doenças não relacionadas, sem evidência clínica ou laboratorial de doença óssea ou hepática. A elevação da fosfatase alcalina varia entre 3 e 50 vezes o limite superior do valor para a idade. A análise das isoenzimas mostra elevação das formas óssea e hepática. Os níveis séricos da fosfatase alcalina retornam ao normal em quatro meses. A elevação sérica da fosfatase alcalina foi relatada em patologias como hiperfosfatasemia familiar persistente assintomática e sintomática e hiperfosfatasemia persistente não-familiar. É indispensável que a HTBI seja considerada no diagnóstico diferencial de um aumento considerável dos níveis séricos de fosfatase alcalina em crianças, sem que seja detectada uma causa óbvia, o que evitará procedimentos desnecessários e dispendiosos durante a investigação diagnóstica.&lt;/span&gt;

Response: Abnormal ALP Isoenzyme in Children with Epilepsy Treated with Carbamazepine

To the Editor: We read with great interest the letter of Okazaki et al. about the abnormal alkaline phosphatase (ALP) isoenzyme in children with epilepsy treated with carbamazepine (CBZ). This drug is actually one of the most frequently prescribed antiepileptic drugs (AEDs); despite a large clinical application, however, the precise mechanism(s) of action of CBZ remains poorly understood as does the pathophysiology of its side effects. A deceleration of skeletal growth and diminished bone mineral density was occasionally reported in some patients treated with CBZ (1,2), but the exact mechanisms of this adverse effect are still unknown. Recently it was demonstrated that CBZ increases ALP activity in the serum of epilepsy patients (3–5); moreover, some researchers found a positive relation between the serum ALP and the serum level of CBZ (6); more recently, O'Hare et al. (7) demonstrated that ALP elevation in patients receiving CBZ had a positive relation with both the duration of treatment and the drug dose. At least six different ALP isoforms exist: one bone/intestinal, two bone, and three liver isoforms; in most of these studies, the fraction of ALP found increased in CBZ-treated patients was the bone isoenzyme, suggesting the presence of an accelerated bone-turnover rate, which is possibly owing to an increased microsomal liver P450 oxidase activity resulting in increased conversion of vitamin D to inactive metabolites and that these epilepsy patients are at greater risk of development of rickets (8). Therefore the report of the three children with epilepsy encountered by Okazaki et al. is of special interest: they found an anomalous ALP isoenzyme band similar to that detected in benign transient hyperphosphatasemia. Although the clinical significance of this anomalous ALP isoenzyme is not clear, if the increase of anomalous ALP isoenzyme is found in other patients, another possible mechanism of the ALP increase due to CBZ action could be supposed.

Viral infection of infants and children with benign transient hyperphosphatasemia.

In this study, we screened serum samples for transient hyperphosphatasemia (TH) using cellulose acetate membrane electrophoresis over a period of 3 years. In the patients found to suffer from TH, we examined the relationship between the clinical condition and viral infection. The frequency of TH was 0.26%, and all of the cases detected were in infants or young children. The female to male ratio of TH was 1.29/1. While there was no clear seasonal fluctuation or periodicity in the appearance of TH, two peaks were recognized in spring and autumn. Research on the clinical manifestations clarified that most of the TH cases had infectious diseases of the upper airways accompanied by symptoms of fever and diarrhea. We examined antibody titers for viruses causing upper airway infectious diseases and identified antibodies for enteroviruses such as Echo 22, Entero 71, and Coxsackie B4. Our results suggested that TH might be caused by an infection of the enterovirus group.