Transient Hyperphosphatasemia Research Articles

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.

Benign Transient Hyperphosphatasemia Associated With Epstein-Barr Virus Enteritis in a Pediatric Liver Transplant Patient: A Case Report

Transient hyperphosphatasemia was found in a 3-year-old male liver transplant recipient. The condition was associated with diarrheal disease due to the Epstein-Barr virus (EBV). Immunosuppression was tapered and valganciclovir prescribed for 3 months, after which the diarrhea resolved and the EBV polymerase chain reaction assays became negative. After 6 months, alkaline phosphatase levels normalized. Isolated elevation of alkaline phosphatase in conjunction with enteric infection is a rare condition. No further diagnostic or therapeutic interventions except treatment of the underlying infection are needed, as this has been shown to be a benign, transient condition.

A new case of transient hyperphosphatasemia in a 21-month-old child with recurrent wheezing – case report

Uvod: Opisuje se slucaj prolazne hiperfosfatazemije u 21-mjesecnog djecaka s ponavljajucom sipnjom tijekom akutnog respiracijskog infekta. Materijali i metode: Određivanje kataliticke aktivnosti alkalne fosfataze provedeno je preporucenom fotometrijskom metodom, a elektroforetsko razdvajanje izoenzima alkalne fosfataze na agaroznom gelu uz obradu seruma lektinom. Rezultati: Tijekom bolnickog lijecenja dijete je imalo povecanu kataliticku aktivnost alkalne fosfataze: prvog dana 4109 U/L, sestog dana 2156 U/L. Pri kontrolnom pregledu 27. dana od prijema u bolnicu aktivnost se smanjila na 505 U/L. Elektroforetskim razdvajanjem izoenzima alkalne fosfataze dokazana je elektroforetska vrpca brža od jetreno-kostanog izoenzima, tzv. brza anodna vrpca. Zakljucak: Pojava izrazito povecane kataliticke aktivnosti alkalne fosfataze uz tipicnu elektroforetsku razdiobu izoenzima u trajanju od nekoliko tjedana ukazuje na prolaznu hiperfosfatazemiju. Pravodobnim prepoznavanjem izbjegava se daljnja nepotrebna dijagnosticka obrada.

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.

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.】

Transient hyperphosphatasemia after pediatric liver transplantation

Transient hyperphosphatasemia of infancy and early childhood is characterized by transiently increased serum activity of alkaline phosphatase (ALP), predominantly its bone or liver isoform, in children under 5 years of age. There is little information on the rate of transient hyperphosphatasemia in pediatric liver transplant recipients. Patients who underwent liver transplantation at Ege University Organ Transplantation and Research Center, Izmir, Tureky, between January 1998 and January 2005, were included in the study. A total of 70 paediatric liver recipients' medical records were analyzed retrospectively. Transient isolated hyperphosphatasemia was observed in two of 70 patients and the rate of transient hyperphosphatasemia was estimated to be 2.8% in pediatric liver transplant recipient. Diarrheal episode was noted prior to the peak ALP activity in both cases. In one case the causative agent was not found, whereas in the other case Rotavirus was detected in a stool specimen. ALP activity normalized at 4 months and 18 days in the first and second cases, respectively. They continue follow up at the outpatient clinics with stable graft function. It is important to know that very high ALP levels can be seen without underlying significant pathology and the benign nature of the condition to avoid unnecessary investigations.

Acute laryngotracheobronchitis and associated transient hyperphosphatasemia: A new case of transient hyperphosphatasemia in early childhood

We report the case of a 20-month old boy with markedly elevated serum alkaline phosphatase (ALP) levels, documented during an episode of acute laryngotracheobronchitis. Biochemical investigations and imaging studies revealed no evidence of bone or liver disease. Transient hyperphosphatasemia (TH) was confirmed when serum ALP levels normalized within 2 months. Several theories were suggested for TH pathophysiology, viral infections among them; the exact causes, however, remain unclear. It is important to recognize TH and avoid misdiagnosis and unnecessary investigations.

A case of transient hyperphosphatasemia of infancy and early childhood in an HIV-positive adult possibly related to atazanavir

A case of transient hyperphosphatasemia of infancy and early childhood in an HIV-positive adult possibly related to atazanavir

Unusually high alkaline phosphatase due to intestinal isoenzyme in a healthy adult

Intestinal alkaline phosphatase (ALP) is more prevalent in individuals of blood group O or B, and increases after a meal, especially on a high-fat diet. We did not realize that clinicians could underestimate the importance of fasting for ALP measurement until one healthy adult showed a huge difference in ALP levels before and after a meal. We report a case of transient hyperphosphatasemia resulting in unnecessary workup due to intestinal ALP in a healthy adult of blood group O.

Hiperfosfatasemia transitória benigna na infância

<span class="texto">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.</span>

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.

Transient hyperphosphatasemia after organ transplantation in children

Transient, isolated hyperphosphatasemia is a rare, benign condition of childhood. Few cases have been described in transplant patients. We report six cases: three after liver transplantation and three after kidney transplantation. Such a phenomenon was found to be as benign after organ transplantation as it is in healthy children. Hence, an isolated increase in the serum alkaline phosphatase level following transplantation should not be of concern in this population of patients.

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.

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.

Transient hyperphosphatasaemia: an important condition to recognize.

To investigate the prevalence and aetiology of transient hyperphosphatasaemia (TH) of infancy and childhood in a tertiary referral paediatric hospital. Retrospective review of the medical records of patients with measured plasma alkaline phosphatase (ALP) activity of over 1000 U/L. Over a period of 1 year, 68 children with plasma ALP activity of over 1000 U/L were identified. The main aetiologies were liver disease (34 cases), TH (21 cases) and bone disease (11 cases). The mean age of children with TH was 1 year and 5 months and there was a male predominance (3:1). The children with liver and bone disease were older (mean ages of 6 years, 6 months and 5 years, 1 month, respectively) and there was no gender difference. The mean plasma ALP activity for the children with TH was 3395 U/L, and in those patients in whom ALP activity was measured sequentially, mean ALP returned to within normal limits after an average of 70 days. There was a seasonal predominance of TH cases, with a significant number presenting during the winter, suggesting a viral aetiology. The most common clinical presentation of children with TH was gastroenteritis (8/21). Cases of TH can be clearly identified by considering the age of the patient and by excluding other known causes of markedly elevated ALP, in particular liver or bone disease. Using these exclusion criteria, the prevalence of TH was found to be high. Early recognition of this benign condition may prevent misdiagnosis and further unnecessary investigations.

Benign Transient Hyperphosphatasemia of Infancy and Childhood

Six children, aged 11 to 25 months, were found to have elevated serum alkaline phosphatase (ALP) levels (1,077 to 9,271 U/L) in the absence of disease. Benign transient hyperphosphatasemia (BTH) was diagnosed when the serum ALP levels returned to normal or decreased significantly within 3 months. Several theories have been suggested regarding the pathophysiology of BTH, but the exact cause is still unclear. We report six cases of BTH and review the literature. It is important to recognize this condition and to avoid extensive and unnecessary evaluation.

Benign Transient Hyperphosphatasemia of Infancy and Childhood

Benign Transient Hyperphosphatasemia of Infancy and Childhood

Transient Hyperphosphatasemia of Infancy and Childhood: Study of 194 Cases

Transient hyperphosphatasemia of infancy and childhood (TH) is a temporary and isolated increase of serum alkaline phosphatase (ALP; EC 3.1.3.1) activity occurring without obvious cause during the first years of life. Despite several reports about this phenomenon, the origin of TH remains obscure. Over a period of 8 years (1992–1999), we detected 194 cases of TH in 106 boys and 88 girls. The hyperphosphatasemia was discovered fortuitously during routine investigations in outpatient and inpatient departments of a children’s hospital with a capacity of 500 beds. A wide variety of clinical disorders was associated with this condition (gastrointestinal diseases, 24%; respiratory infections, 21%; congenital anomalies and …

ROTAVIRUS INFECTION AND DIARRHEA RESULTING IN TRANSIENT HYPERPHOSPHATASEMIA WITH NO EVIDENCE OF LIVER OR BONE DISEASE

99 A temporary elevation of serum alkaline phosphatase (ALP) activity up to 70 times the upper normal value for age without evidence of liver or bone disease is known as "benign transient hyperphosphatasemia of infancy and childhood". The role of infectious agents has been suggested. We report three girls (10-28 months) with diarrhea and rotavirus infection who had severe hyperphosphatasemia (1033, 2589, 2764 U/L). They had normal serum calcium, phosphorus, parathyroid hormone, and 1,25 dihydroxycholecalciferol levels. Their bone radiogram revealed no rickets. Serum transaminases. gamma-glutamyl transferase, lactate dehydrogenase, 5′ nucleotidase, and bilirubin levels were normal. Two of them had a small bowel biopsy that was normal. The ALP isoenzymes were predominantly of skeletal origin in all subjects. With no evidence of bone or liver disease, serial measurement of serum ALP levels revealed a spontaneous normalization (ALP: 149-246 U/L) within 16 to 42 days, and there was no sequelae. This benign transient hyperphosphatasemia may be associated with or induced by diarrhea or rotavirus infection. The mechanism of elevated serum ALP levels remains elusive. An acute infection in the presence of diarrhea may lead either to decreased clearance or to increased production of skeletal ALP isoenzymes secondary to hyperactivated osteoblasts. When the level of hyperphosphatasemia is significantly greater than what is expected from rickets or cholestasis, children younger than 5 years who have rotavirus infection require serial measurement of ALP levels only. However, if ALP remains elevated after 8 weeks of the initial determination, further studies become indicated. Awareness of this phenomenon will curtail expensive and extensive investigations.