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Background The incidence of a bifid electrophoretic pattern in the albumin region on serum protein electrophoresis is an infrequent phenomenon. The availability of literature from India is scarce and is limited to case reports. Objective The aim of the study is to analyze the frequency of bisalbuminemia in an Indian referral facility. The study delved into their clinical associations. Material and Methods The retrospective case records of the patient from the departmental database were scrutinized. The study subjects were for an 8-year study period. Results There were about 39,900 serum electrophoresis performed in an 8-year study period. A total of 40 cases of bisalbuminemia were detected. The incidence in our cohort was 0.01%. Conclusion Bisalbuminemia, an overtly benign condition, is infrequent in Indian population although not rare. It is associated with several clinical disorders; however, the association seems to be plausibly coincidental.

A 5-year-old spayed, crossbred female dog was referred for a unilateral nosebleed of 4 months’ duration. Rhinoscopy revealed significant inflammation of the nasal mucosa compatible with severe rhinitis. On the right nostril, the presence of a white patch on the mucosa was observed and a biopsy was taken. Histopathology revealed a granulomatous inflammation with the presence of neutrophils and lymphocytes. Some macrophages contained small oval microorganisms compatible with Leishmania species. The presence of Leishmania infantum was confirmed by specific immunohistochemistry, showing stained intracellular microorganisms. Abnormal clinicopathological findings included mild anaemia and hyperglobulinemia with polyclonal gammopathy. Moderate amount of antibodies to L. infantum were detected by ELISA in serum. An anti-Leishmania therapeutic protocol was established with allopurinol and meglumine antimoniate, and 4 months later, a follow-up examination was performed showing improvements in laboratory parameters with the exception of the presence of bisalbuminemia.

L'électrophorèse des protéines sériques revêt un intérêt diagnostic certain. Nous rapportons un cas associant une électrophorèse insolite à une cholestase ictérique compliquant un cholangiocarcinome. Il s'agit d'un patient âgé de 55 ans hospitalisé pour l'exploration d'un ictère cholestatique. L'électrophorèse capillaire a montré une bis-albuminémie objectivée par l'épaississement du bas du pic de l'albumine, et un pic surnuméraire X. Une seconde électrophorèse sur Hydragel a montré la disparition des deux anomalies précitées qui est la preuve de l'origine acquise de cette bis-albuminémie et de la nature lipidique du pic X. L'étiologie la plus probable dans notre cas est la présence de substances interférentes telles que la bilirubine libre (hyperbilirubinémie), les lipides (hyperlipémie) et les acides biliaires. Un tableau de bis-albuminémie dans un tracé électrophorétique similaire à notre cas, devrait suscitée la recherche de pathologies sous-jacentes.

Zusammenfassung Ausgehend von der kasuistischen Beobachtung einer zweigipfligen Albuminbande in der Serumproteinelektrophorese wird die Bisalbuminämie als angeborene oder erworbene Proteinanomalie nach Durchsicht der Literatur in einer Kurzübersicht dargestellt. Nach einer Einführung zur Bisalbuminämie werden deren Nachweismethoden, funktionelle und klinische Bedeutung sowie Befundinterpretation behandelt. Bei der Bisalbuminämie handelt es sich um eine seltene neutrale Normvariante ohne Symptom- bzw. Krankheitswert, die keiner weiteren Abklärung bedarf.

Introdução: A bisalbuminémia é uma alteração qualitativa da albumina e define-se pela coexistência no mesmo indivíduo de dois tipos de albumina sérica com mobilidade eletroforética diferente. Existem duas formas: hereditária e permanente ou adquirida e transitória.Caso Clínico: Adolescente, sexo feminino, 17 anos, referenciada à consulta hospitalar por achado incidental de bisalbuminémia detetada na eletroforese de proteínas plasmáticas, realizada em contexto de noção de diminuição da força dos membros inferiores. O exame objetivo não apresentava alterações. Foi excluída causa secundária de bisalbuminémia. Posteriormente, confirmou-se a mesma alteração em eletroforese de proteínas plasmáticas realizada ao irmão de 14 anos e à mãe.Discussão: Descrevemos um caso raro de bisalbuminémia hereditária numa família portuguesa. Em geral não apresenta significado patológico, no entanto tem interesse para o clínico o conhecimento desta alteração analítica para melhor orientar e esclarecer os seus doentes.

L'électrophorèse des protéines sériques (EPS) est une analyse de routine dans la pratique quotidienne d'un laboratoire de biologie médicale. Le but de notre étude est d’analyser les différents profils électrophorétiques rencontrés dans notre pratique courante. Nous avons mené une étude transversale portant sur 410 échantillons sériques qui ont été collectés dans le cadre de l’analyse de routine au sein du laboratoire de biochimie du Centre Hospitalier Universitaire (CHU) Mohammed VI d’Oujda. L’électrophorèse des protéines sériques a été réalisée sur automate Capilarys2 Flex piercing de Sebia. 241 sérums de femmes et 169 sérums d’hommes ont été collectés. Âgés de 1 à 91 ans avec une moyenne d’âge de 49 ans. 19,5% des EPS étaient normales, l’hypo-albuminémie a été noté chez 34% des cas, un syndrome inflammatoire chronique dans 19,5% des cas, un syndrome néphrotique chez 2% des cas, 5,8% de nos patients avaient un bloc béta-gamma, une hypogammaglobulinémie a été observée dans 8,5% des cas, et 29 pics monoclonaux ont été notés, une bis-albuminémie a été objectivée chez 2 patients. Sur les 410 prélèvements: 92 immunofixations ont été réalisées dont 23 étaient positives (objectivant une gammapathie monoclonale). Cette étude met en évidence la variabilité des motifs de prescription d’une électrophorèse des protéines sériques, ainsi que l’importance des données cliniques pour une interprétation meilleure.

Bisalbuminemia is a rare condition characterized by abnormal electrophoretic pattern of serum albumin. There are two types of bisalbuminemia – hereditary and acquired. The acquired type has been reported in chronic renal diseases, pancreatitis, and in patients using beta-lactam antibiotics. The aim of this case report is to discuss the clinical significance of bisalbuminemia in a 58-year-old African male with sickle cell anemia. How to cite this article Chakravarthy SN, Ramanathan S, Menon S, Durairaj M. Bisalbuminemia in an African Male with Sickle Cell Disease. Indian J Med Biochem 2017;21(1):69-71.

La bisalbuminemie, qu’elle soit hereditaire ou acquise, represente une anomalie electrophoretique rare de l’albumine, caracterisee par un dedoublement de la fraction d’albumine sur le trace d’electrophorese des proteines seriques. Ce dedoublement traduit la presence chez un meme individu d’une albumine plasmatique normale et d’une albumine modifiee. Nous decrivions le cas d’une patiente de 62 ans hospitalisee au service de medecine interne de l’HMIMV pour metastases hepatiques d’un adenocarcinome digestif et dont l’electrophorese des proteines seriques (EP) realisee sur capillaire (Capillarys de la societe Sebia) revele une bisalbuminemie. L’enquete familiale a permis d’exclure ce caractere hereditaire de la bisalbuminemie pour retenir l’aspect acquis. La bisalbuminemie acquise, en dehors de traitement par de fortes doses de betalactamines, de pancreatite chronique avec rupture d’un pseudokyste ou de la fixation d’une immunoglobuline monoclonale sur l’albumine chez des sujets atteints de myelome est un evenement exceptionnel. Le mecanisme physiopathologique dans le cas rapporte demeure inexplique, comme c’est d’ailleurs le cas des bisalbuminemies acquises associees a d’autres contextes pathologiques (maladie d’Alzheimer, syndrome nephrotique). Au meilleur de notre connaissance, la bisalbuminemie dans les metastases hepatiques d’adenocarcinome digestif n’a pas ete rapportee jusqu’a ce jour, d’ou l’importance du cas rapporte.

Background: Hemoglobin A1c (HbA1c) is considered the gold standard for assessment of glycemic control in diabetic patients. HbA1c is inadequate in individuals homozygous or compound heterozygous for hemoglobin variants or in conditions with an altered red blood cell turnover. In these cases glycated albumin (GA) is proposed as an alternative assay. We aimed to evaluate the analytical performance of the Diazyme glycated serum protein (GSP) assay on an automated analyzer, to establish a reference interval (RI), and to compare from a clinical perspective, GSP/GA with glycated Hb (glyHb) results. Methods: Validation studies followed the CLSI guidelines and included precision, linearity, interferences, concordance of results with glyHb, and RI calculation. GSP was analyzed on representative samples with previously ordered HbA1c and albumin from the Dyna LIFEDX laboratory. Samples from patients with bisalbuminemia, hemoglobinopathies, and multiple myeloma were also included. Results: Within-run and total imprecision was 2 = .91, kappa = .78, P = .167). GSP RI was 160 to 340 μmol/L or if expressed as %GA 10.5 to 17.5%. Conclusion: Analytical performance of the Diazyme GSP assay on the Siemens ADVIA 1800 is acceptable for clinical use. The RI obtained was higher than that suggested by the manufacturer.

Bisalbuminemia is an uncommon finding that is seen as bifid albumin peak on serum protein electrophoresis. We report here this unusual finding in an adult male diagnosed with multiple myeloma on routine workup.

Hereditary bisalbuminemia is an asymptomatic and heterozygous condition in a range of species characterized by the presence of two serum albumin fractions with different electrophoretic mobility resulting in a bicuspid pattern on serum electrophoresis. Bisalbuminemia has been diagnosed by electrophoresis in two bottlenose dolphin (Tursiops truncatus) families, but causative mutations and the inheritance pattern have not been identified. The aims of this work are: to investigate polymorphisms of the bottlenose dolphin albumin gene and to identify mutations causative of bisalbuminemia; to identify the inheritance pattern in two bottlenose dolphin families. Coding regions of the albumin gene were screened for mutations in 15 bottlenose dolphins kept under human care from two distinct families. Eighteen albumin mutations (three synonymous and 15 non-synonymous) were identified. Two non-synonymous variations co-segregated with bisalbuminemic phenotype: p.Phe146Leu in exon 4 and p.Tyr163His in exon 5. The amino acid change in exon 5 was associated with the secondary and/or tertiary structure variation of the protein and has been reported as causative of bisalbuminemia in humans. Pedigree analysis of the dolphin families showed an autosomal codominant inheritance pattern. In this work, the mutations potentially responsible for bisalbuminemia were identified and confirmed the autosomal codominant trait in bottlenose dolphins.

Background Hereditary bisalbuminemia is a relatively rare anomaly characterized by the occurrence of two albumin fractions on serum protein separation by electrophoresis. In human medicine, it is usually revealed by chance, is not been clearly associated with a specific disease and the causative genetic alteration is a point mutation of human serum albumin gene inherited in an autosomal codominant pattern. This type of alteration is well recognizable by capillary zone electrophoresis (CZE), whilst agarose gel electrophoresis (AGE) not always produces a clear separation of albumin fractions. The aims of this study is to report the presence of this abnormality in two separate groups of related bottlenose dolphins and to compare the results obtained with capillary zone and agarose gel electrophoresis. Results Serum samples from 40 bottlenose dolphins kept under human care were analyzed. In 9 samples a double albumin peak was evident in CZE electrophoresis while no double peak was noted in AGE profile. Since only an apparently wider albumin peaks were noted in some AGE electrophoretic profiles, the ratio between base and height (b/h) of the albumin peak was calculated and each point-value recorded in the whole set of data was used to calculate a receiver operating characteristic curve: when the b/h ratio of albumin peak was equal or higher than 0.25, the sensitivity and specificity of AGE to detect bisalbuminemic samples were 87 and 63 %, respectively. The bisalbuminemic dolphins belong to two distinct families: in the first family, all the siblings derived from the same normal sire were bisalbuminemic, whereas in the second family bisalbuminemia was present in a sire and in two out of three siblings. Conclusions We report for the first time the presence of hereditary bisalbuminemia in two groups of related bottlenose dolphins identified by means of CZE and we confirm that AGE could fail in the identification of this alteration.

Background: Protein electrophoresis is widely applied in veterinary medicine, but is not used often in reptiles, in part because of lack of reference values. Objective: The goals of this study were to compare plasma protein profiles obtained by cellulose acetate electrophoresis (CAE) and agarose gel electrophoresis (AGE), measure precision and examine interference by sample hemolysis, and establish preliminary reference intervals for 2 reptile species. Methods: Heparinized plasma samples from healthy and diseased adult female Iguana iguana (n=40) and Trachemys scripta (n=60) were analyzed by CAE and AGE. Total protein concentration was measured by the biuret method. Electrophoresis results were compared using Bland–Altman plots and Passing–Bablok regression analysis. Precision and the effects of sample hemolysis were determined. Results from clinically healthy animals were used to determine reference intervals. Results: Five protein fractions were identified in both species, with bisalbuminemia observed in 23/40 iguanas. High correlation was observed between the 2 methods for all fractions, with few proportional and systematic errors. Coefficients of variation were lower using AGE vs CAE and for I. iguana vs T. scripta. Two additional bands were observed in hemolyzed samples from T. scripta; 1 additional band was observed for I. iguana. Minimum and maximum values were reported for healthy I. iguana (n=14) and T. scripta (n=22). Conclusions: Although both methods are acceptable, the performance of AGE was slightly better than that of CAE for analysis of plasma from reptiles. Furthermore, reptile electrophoretic patterns should be interpreted based on the method used, the species analyzed, and the quality of the plasma sample.

Case reports of bisalbuminemia (patient serum containing albumin A and an albumin variant differing by single amino-acid substitutions) have included different races or ethnic groups and are often reported in association with various pathologic states. Here, we describe a 70-year-old woman with vague symptoms, the most concerning of which was worsening vision with retinal hemorrhages found on exam. During the workup, serum protein electrophoresis was performed demonstrating a prominent monoclonal component (IgM kappa) and bisalbuminemia as an incidental finding. This represents the first reported case in the literature of the coexistence of bisalbuminemia and Waldenstrom macroglobulinemia. The possibility exists that some endogenous or pharmacologic substances may interact differently with albumin variants as compared with normal albumin; however, the finding of bisalbuminemia did not influence the diagnosis, management, course, or prognosis of this patient’s lymphoma.

Bisalbuminemia is a rarely encountered anomaly characterized by presence of bifid albumin bands or a single widened albumin band in electrophoretogram. Inherited bisalbuminemia is quite rare and inherited as an autosomal dominant form. The acquired form of bisalbuminemia is usually transient and may be observed during long term beta lactam antibiotic therapy, acute pancreatitis, myeloma and nephrotic syndrome. This is a case of bisalbuminemia in 61-year-old diabetic female with hypothyroidism came with acute exacerbation of bronchial asthma.

Background Serum or plasma protein electrophoresis is used as a routine test for health assessment in veterinary medicine, but there are only a limited number of studies regarding clinical use of electrophoresis in reptile species. Objective The goals of this study were to establish reference intervals for plasma protein electrophoresis in the Green Iguana (Iguana iguana), compare values between males and females, and to identify season-related changes. Methods Plasma samples were obtained from 21 healthy captive male and female Green Iguanas. Agarose gel electrophoresis was performed using an automated Hydrasys system. Results Four main protein fractions were observed: albumin, α globulins, β globulins, and γ globulins. Bisalbuminemia was observed in 4 of 21 healthy iguanas. Minimum and maximum values were reported for healthy Green Iguanas in March, June, September, and December. Seasonal changes in albumin were determined between March and December, and in γ globulins between June and September. Differences between males and females were seen in albumin concentration in September. Conclusions Reference intervals of the plasma protein fractions according to electrophoresis in the Green Iguana can be affected by seasonal changes and sex of animals. It should be taken into account when clinical evaluation is performed.

We investigated whether the electrophoretic patterns and clinical information derived from the five principal fractions of the Beckman Paragon capillary zone electrophoresis (CZE) 2000 system are comparable to the results obtained by the cellulose acetate electrophoresis (CAE: Olympus AES 320) system. Concordance studies between the results obtained by CAE and CZE were performed on sera from pregnant women and from patients with nephrotic syndrome, acute and chronic inflammatory diseases, cirrhosis, monoclonal and polyclonal gammopathy, and bisalbuminemia. In all subjects except for the pregnant women, the results of CAE and CZE agreed 100% in terms of percent composition for albumin, and α1- and α2-globulins. Concordance for γ-globulin was 92-100% in terms of both percent composition and absolute concentration. Three discordant cases according to the results for β-globulin by CAE and CZE were found in patients with monoclonal gammopathy, who also showed discordant results for γ-globulin. An M-protein spike observed in either the β-globulin or γ-globulin fraction was 100% detected by both CAE and CZE analyses. In another six discordant cases for the β-globulin fraction observed in patients with cirrhosis and polyclonal gammopathy, part of the tail of the β-globulin fraction tended to be measured as γ-globulin by CAE. In three of the four bisalbuminemia cases, the double band of albumin observed by CZE was not detected by CAE. The results show that the electrophoretic patterns and clinical information derived from the five principal fractions of the Beckman Paragon CZE 2000 system are comparable to the results obtained by classical CAE.

Background The aim of the present work was to characterize the molecular defects of a slow-migrating (albumin Zagreb) and a fast-migrating (albumin Krapina) genetic variant of human serum albumin detected in heterozygous persons living in Croatia and to elucidate the fatty acid-binding properties of the two alloalbumins. Methods Purification and structural identification of the variants were performed by conventional protein chemistry methods, whereas types and amounts of albumin-bound, endogenous fatty acids were determined by gas chromatography. Results Protein sequencing established that albumin Zagreb is a proalbumin variant (−1Arg→Gln), and that albumin Krapina is due to a mutation within the mature polypeptide chain (573Lys→Glu). The gas chromatographic results showed that the fatty acid-binding properties of the proalbumin variant are normal, while the amino acid substitution in position 573 resulted in a general decrease of fatty acid binding. Conclusions The structural defects of the first alloalbumins, detected by routine clinical electrophoresis among the Croatian population, were characterized. Albumin Zagreb is caused by a hot-spot mutation occurring in a CpG sequence in the albumin gene. It is commonly assumed that bisalbuminaemia has no direct clinical relevance. However, the present study suggests that naturally occurring mutations can affect the ligand-binding properties of human serum albumin.

Hereditary and acquired bisalbuminemia, in which the serum contains an albumin variant differing from albumin A by single amino-acid substitutions, have been reported in different races or ethnic groups and in association with various pathologic states. The importance of this rare condition in the pathophysiology of established diseases is uncertain. We evaluated a 68-year-old woman with chronic kidney disease who presented with worsened serum creatinine concentration despite lack of dietary or medical changes. Serum protein electrophoresis was performed with an automated rapid electrophoresis system. Bisalbuminemia was noted as an incidental finding on serum protein electrophoresis. The serum creatinine level stabilized with dietary protein restriction and a beta-blocking agent/diuretic combination for blood pressure control. Although the possibility that some physiologic or pharmacologic substances may not bind to abnormal albumin variants as well as they bind to normal albumin should not be discounted, the finding of bisalbuminemia did not influence the diagnosis, management, course, or prognosis of chronic kidney disease. The role of persistent bisalbuminemia in renal disease is uncertain.

The capillary electrophoresis is a very powerful separation method offering a high degree of resolution. However, certain interferences can be detected giving transitory shoulders or peaks. We report the case of a serum protein electrophoresis performed with Capillarys (Sebia) in a 68-year-old patient, hospitalized for cancer of the head of the pancreas, which showed an important shoulder in the migratory range of albumin, simulating bisalbuminemia. An interference with alphafetoprotein was proven explaining this electrophoretic aspect.

Plasma from a patient with chronic pancreatic pseudocyst showed an additional more negative albumin band (18%) on agarose gel electrophoresis. Both components bound (63)Ni(2+), indicating intact N-terminals; however, electrospray ionisation analysis of the intact proteins showed the mass of more negative albumin was 1254 Da less than the control and that the apparently normal band was 112 Da less. Reverse phase mapping and mass analysis of CNBr peptides showed three proteolytically modified forms of the C-terminal peptide indicating that some 81% of the albumin molecules lacked the C-terminal Leu residue, that 18% lacked the C-terminal KKLVAASQAALGL and that approximately 1% lacked the QAALGL sequence. These findings were further verified by tryptic mapping of the aberrant CNBr peptides. The truncations probably result from exposure of the albumin to 'leaking' pancreatic endo and exoproteases. During less acute phases of the disease, the 13 and 6 residue truncated forms together decreased to less than 1%, while the des-Leu(585) form made up the balance; no normal albumin was detected. This suggested that the des-Leu(585) form might be present at low levels in the plasma of normal individuals and CNBr mapping confirmed that it constituted 4-15% of the albumin from normal plasma.

The molecular defects of three different slow-migrating genetic variants of human serum albumin, albumins Kamloops (formerly RIH), Stirling and Amsterdam, previously characterized only by electrophoretic and dye-binding studies, are now reported. Two of them are proalbumin variants: sequential analysis of the purified whole proteins has established the mutation responsible for albumin Kamloops as -1Arg-->Gln, and for albumin Stirling as -2Arg-->His. A Glu-->Lys substitution in position 570 of the mature albumin molecule was determined in albumin Amsterdam by sequential analysis of two abnormal tryptic fragments. The three alloalbumins are caused by single-base changes all of which seem to represent hot-spots in the albumin gene. The possible functional consequences of the presence of a circulating alloalbumin are discussed.