The significance of isolated aspartate aminotransferase elevation in healthy paediatric patients.

AIM: Aspartate aminotransferase (AST) is an enzyme expressed in several organs; therefore, AST elevation may reflect outside of liver pathology. AST elevation may also be associated with macro-AST (m-AST). The aim of this study was to evaluate the long-term course of children with prolonged isolated AST elevation and the prevalence of m-AST in our cohort. METHODS: We retrospectively reviewed the medical charts of children diagnosed with prolonged isolated AST elevation and were evaluated for m-AST. RESULTS: Thirty-two patients were included. AST elevation persisted for a median of 66.6 months and ranged from 1.23 to 12-fold upper limit of normal (ULN). Twenty-two percent were m-AST positive and 44% had borderline levels of m-AST. A statistically significant difference was found for age at presentation between the borderline and the positive m-AST groups (31 vs. 69 months, respectively. p = 0.045). None of the patients with elevated AST developed significant liver disease. CONCLUSION: We confirm the benign course of prolonged isolated AST elevation in general and m-AST in particular. A fifth of the patients with isolated AST elevation were m-AST positive. No differences have been found in AST levels between negative, borderline or positive m-AST.

Persistent elevation of aspartate aminotransferase in a child after incomplete Kawasaki disease: a case report and literature review.

BACKGROUND: Interpretation of abnormalities in liver function tests, especially in asymptomatic children, is a common problem faced by clinicians. Isolated elevation of aspartate aminotransferase may further puzzle physicians. Macro-aspartate aminotransferase (AST) results from complexes AST produces with other plasma components, such as immunoglobulin. To our knowledge, this is the first report on a case of macro-AST-associated incomplete Kawasaki disease (KD). It is to make physicians aware of this benign condition and help to prevent extensive, unnecessary investigations and invasive workups. CASE PRESENTATION: A 16-month old boy with a 7-day history of fever was admitted to our pediatric ward for pyrexia workup. After complete investigations, KD was confirmed by a pediatric rheumatologist. During his admission and serial follow-up tests, an isolated AST elevation was noted. Comprehensive tests were performed and using the polyethylene glycol (PEG) precipitation method, macro-AST was confirmed. The patient has been followed up for 3 years, and so far, the benign nature of this condition has been confirmed. CONCLUSION: Clinicians should consider testing for macro-AST when elevated AST is the only abnormal lab finding. Although an uncommon finding, macro-AST may be seen in both children and adults. There are many reasons for this phenomenon, including resolved acute hepatitis or in some cases, inflammatory bowel disease, hepatic malignancy, monoclonal gammapathy, celiac disease, or KD; however, it may be observed in asymptomatic healthy children as well. Using the PEG precipitation method, a definitive diagnosis can be made. In none of these conditions does macro-AST have any prognostic significance. An appreciation of macro-AST may prevent the need for more invasive investigations to which patients may be unnecessarily subjected. It is important to recognize this condition as benign and assure patients that no specific treatment is required.

Isolated elevation of aspartate aminotransferase (AST) in an asymptomatic patient due to macro-AST.

BACKGROUND: A rare and benign cause of isolated aspartate aminotransferase (AST) increase is due to the presence of macro aspartate aminotransferase (macro-AST). Macro-AST is not usually considered by clinicians, leading to a large number of unnecessary and even invasive tests before diagnosed. Most commonly used laboratory methods for detection of macro-enzymes are precipitation with polyethylene glycol (PEG), ultracentrifugation and gel filtration chromatography (GFC). METHODS: We report a case of an asymptomatic patient with persistent isolated AST elevation. PEG precipitation and an alternative method based on the low stability of this macro-enzyme were performed on the patient serum. RESULTS: Macro-AST was early detected by the laboratory observing a significant decrease in AST concentrations when the serum is stored at 4ºC. CONCLUSIONS: Macro-AST detection based in this method can be very useful as screening, especially in those laboratories where other technologies are not available. Macro-AST must be considered as cause of unexplained isolated AST elevations before prior investigations to avoid the consequent cost and potential harm to the patient. In our case, early detection of macro-AST with this method avoided unnecessary treatment and invasive test such as liver biopsy.

A heterozygous mutation in GOT1 is associated with familial macro-aspartate aminotransferase.

BACKGROUND & AIMS: Macro-aspartate aminotransferase (macro-AST) manifests as a persistent elevation of AST levels, because of association of the protein with immunoglobulins in the circulation. Macro-AST is a rare, benign condition without a previously confirmed genetic basis. METHODS: Whole exome sequencing (WES)-based screening was performed on 32 participants with suspected familial macro-AST, while validation of variants was performed on an extended cohort of 92 probands and 1,644 healthy controls using Taqman genotyping. RESULTS: A missense variant (p.Gln208Glu, rs374966349) in glutamate oxaloacetate transaminase 1 (GOT1) was found, as a putative causal variant predisposing to familial macro-AST. The GOT1 p.Gln208Glu mutation was detected in 50 (54.3%) of 92 probands from 20 of 29 (69%) families, while its prevalence in healthy controls was only 0.18%. In silico analysis demonstrated that the amino acid at this position is not conserved among different species and that, functionally, a negatively charged glutamate on the GOT1 surface could strongly anchor serum immunoglobulins. CONCLUSIONS: Our data highlight that testing for the p.Gln208Glu genetic variant may be useful in diagnosis of macro-AST. LAY SUMMARY: Higher than normal levels of aspartate aminotransferase (AST) in the bloodstream may be a sign of a health problem. Individuals with macro-AST have elevated blood AST levels, without ongoing disease and often undergo unnecessary medical tests before the diagnosis of macro-AST is established. We found a genetic variant in the GOT1 gene associated with macro-AST. Genetic testing for this variant may aid diagnosis of macro-AST.

Macroenzymes as a reason for aminotransferases flare in cystic fibrosis patients on CFTR modulators therapy - Report of three cases.

It has been shown that macro-ALT/macro-AST cause false increase of ALT/AST activity in standard laboratory testing. This short communication presents a group of cystic fibrosis subjects who developed aminotranferases flare a few months after initiation of CFTR modulators therapy. Patients did not present any clinical signs or symptoms of liver failure and differential examination did not show any underlying liver disease. All patients tested positive for macro-ALT and macro-AST. Despite increased and fluctuating ALT/AST activity in standard tests patients restarted CFTR modulators therapy with good clinical effect and do not present any other than hypertransaminasemia signs or symptoms of progressing liver disease. Our data shows that ALT/AST flare during CFTR modulators therapy may be related to macro-ALT/macro-AST, thus patients with high ALT/AST during CFTR modulators therapy should be tested for macro-ALT/macro-AST.

Macro-Aspartate Aminotransferase and Its Laboratory Detection: A Case Report.

Background: Increased enzyme activity in human blood serum is usually associated with the existence of disease. On the other hand, enzyme activity can also be elevated in the presence of benign conditions, such as macro-enzymes. Macro-enzymes could lead to highly unnecessary and invasive procedures which may cause complications to the patient and an extra cost for the hospital. Therefore, it is important to diagnose this condition in order to avoid unnecessary clinical tests. Case Presentation: We present a case of a 71-year-old asymptomatic female with persistent elevation of AST who was referred to our hospital for additional testing for underlying liver disease. By using polyethylene glycol (PEG) precipitation assay, we were able to identify macro-AST. This helped to avoid the high-risk liver biopsy procedure. Conclusion: In the case of an isolated elevation of AST activity with no clinical indications of liver disease, diagnostic work-up for macro-AST should always be considered by physicians.

Persistently high serum aspartate aminotransferase level in an asymptomatic young patient.

Key Clinical Message: We report a young man with isolated elevated AST. He had no other evidence of liver or other related diseases. All the tests and examination reports were negative. The final diagnosis of macro-AST was confirmed by PEG precipitation tests. Abstract: Elevated liver enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), may commonly indicate liver injury. However, macro-AST is generally a benign condition that may be considered as pathologic by clinicians. A young man with isolated elevated AST for more than 10 years who have taken extensive tests and examinations was diagnosed with macro-AST in our article. Thus, in patients with isolated AST-elevation, polyethylene glycol (PEG) precipitation test was recommended to test whether macro-AST could be diagnosed.

[Clinical, biochemical and epidemiological features of macro-AST preceding inflammatory bowel disease diagnosis by several years]. / Caractéristiques cliniques, biochimiques et épidémiologiques d'une macro-ASAT précédant le diagnostic de maladie inflammatoire chronique de l'intestin de plusieurs années.

INTRODUCTION: An isolated elevation of aspartate aminotransferase (AST) is a diagnostic issue. Macro-aspartate aminotransferase (macro-AST) corresponds to the formation of complexes between AST and immunoglobulins. CASE REPORT: We report the case of a patient with macro-AST identified several years before the onset of inflammatory bowel disease (IBD). A 6-year retrospective analysis in our laboratory identified only one case out of 42 540 adult patients. CONCLUSION: The objective of this work is to increase awareness of this benign disorder among clinicians and biologists, as well as to aid in prescribing only the required tests.

Importance Of Laboratory Detection Of Macro-Aspartate Aminotransferase.

The macroenzyme form of aspartate aminotransferase (macro-AST) is formed by the binding of AST with immunoglobulins. Macro-AST excretion from serum is prolonged because of its high molecular weight, leading to increased AST activities. Because of the difficulty in detecting macro-AST through routine laboratory tests, affected patients often undergo repeated examinations, with associated anxiety. We report a case in which macro-AST was detected by assaying the patient's serum after refrigeration at 4ºC for 3 days. The sample showed progressive loss of AST activity compared with that frozen in the refrigerator, indicating the presence of macro-AST, which was confirmed as a complex with IgG-κ. The cold storage method was validated using many samples obtained from several patients. Use of this simple method to detect macro-AST may avoid unnecessary examinations and patient anxiety even at primary care facilities.

[Macro-AST and myeloma: An incidental association?] / Macro-ASAT et myélome : une association fortuite ?

INTRODUCTION: Macro-AST is recognized as a classical aetiology of isolated and persistent increase of serum aspartate aminotransferase (AST) levels. Macro-AST are high molecular weight complexes associating AST and a macromolecule, often an immunoglobulin. Although those macroenzymes of unknown pathogenesis are usually non-pathogenic, association with several diseases, including autoimmune diseases and liver diseases has been described. CASE REPORT: We report here the case of a 45-year-old patient with previously normal liver enzymes in whom an AST elevation and an IgA monoclonal gammopathy were discovered concomitantly. Following the diagnosis of multiple myeloma, we could evidence in the patient's serum a complex between AST and the monoclonal IgA. AST levels course followed closely the progression of monoclonal gammopathy. CONCLUSION: This is the first report demonstrating a clear link between macro-AST and a monoclonal gammopathy.

Persistently raised aspartate aminotransferase (AST) due to macro-AST in a rheumatology clinic.

Macrocomplexes between immunoglobins and aspartate aminotransferase (macro-AST) may result in persistently increased AST concentration. The presence of macro-AST in patients has been implicated in unnecessary investigations of abnormal liver function tests. We report the case of a 44-year-old female who presented to the rheumatology clinic with a 12-months' history of constant widespread pain affecting her limbs and was found to have an elevated AST concentration. Further information from her GP revealed a 14-years' history of elevated AST with otherwise normal liver function. Previous abdominal ultrasound and two liver biopsies carried out 2 years apart were normal. This prompted further analytical investigation by the biochemistry department which identified macro-AST as the cause. This case illustrates that persistently raised isolated AST concentration with no other abnormal indices may warrant macroenzyme analysis potentially avoiding unnecessary invasive investigations.

Macro-AST as a cause of hypertransaminasemia: an uncommon entity but it exists

Macroenzymes are complexes formed by the binding of enzyme molecules to each other or to other plasma components. We report the clinical case of a woman with abnormal liver enzymes secondary to macro-AST. Macro-AST should be considered in the differential diagnosis as a cause of isolated AST elevation, thus avoiding unnecessary additional tests. (AU)

Macro-aspartate Aminotransferase in a Patient with Chronic Hepatitis C / 대한소화기학회지

Macroenzymes are normal enzymes complexed with an immunoglobulin (usually IgG, rarely IgA or IgM). A number of macroenzymes have been reported in the literature. Among them, macro-AST has been detected in diseases such as acute and chronic hepatitis, various malignancies and autoimmune diseases, but usually not associated with any specific disease. We report a case of elevated AST activity in serum due to marco-AST formation in a female with chronic hepatitis C which was confirmed by AST isoenzyme electrophoresis. To our knowledge, this is the first report of macro-AST occurred in chronic hepatitis patient in Korea.