Report and Abstracts of the Joint Annual Congress of the AMBQ-CAMB 2009

The second joint congress of l’Association des Médicins Biochimistes du Québec (AMBQ) and the Canadian Association of Medical Biochemists (CAMB) was held this year from October 7 to 9 in Montreal. The setting was the picturesque Hôtel Place d’Armes, which is situated in the historic Old Montreal district. There were over 60 attendees comprising both Specialists and Medical residents-in-training and representing the breadth of Canada from the Atlantic to the Pacific. The scientific committee composed of Dr. Jean. Dubé (Centre Hospitalier U. de Sherbrooke), Dr. Bernard Fruteau-de-Laclos (Centre Hospitalier AUQ), Dr. Élaine Letendre (Centre Hospitalier U. de Montreal), Dr. Bassam A. Nassar (Capital Health) and Dr. Claude Petitclerc (CHUM) arranged a series of informative and interesting scientific sessions. Day 1 saw a training session for the medical residents conducted by Dr. Yves Giguère (Centre Hospitalier de l’U. Laval) on Prenatal Screening. A meeting of the specialty committee of the Royal College for Medical Biochemistry followed this. A major topic of this meeting was the re-alignment of the training requirements. Day 2 began with the business meeting of the AMBQ. The scientific sessions began later that day with a session on “Pharmacotoxicology and the Role of the Laboratory” chaired by Drs. Andre Mattman (B.C. Children & Women’s Health Centre) and Bassam A. Nassar. The first speaker, Dr. Margaret Thompson (Hospital for Sick Children), in her talk “Clinical Toxicology – for the Laboratory” reviewed the role of the Ontario Poison Centre, which may serve as a model for the rest of the country. This was followed by Dr. Zulfikarali Verjee (HSC), who is clearly a master of the subject, with his talk, “Challenges in Urine Drug Screens: Ongoing Issues”. The morning session ended with Dr. Andre Mattman’s presentation “Heavy Metal Toxins – How and Why to Test in the Clinical Laboratory”. Day 3 moderated by Dr. Élaine Letendre (CHUM) focused on risk factors for cardiovascular disease. The first speaker in the morning was Dr. Jacques Genest Jr. (McGill University Health Centre) who reviewed the new Canadian guidelines for the diagnosis and treatment of dyslipidemias. He described in detail the thinking behind the new guidelines. This was followed by a presentation by Dr. Allan Jaffe (Mayo Clinic) who gave the audience a most authoritative description of the soon to be introduced fourth generation high sensitivity assays for troponins. These assays will have a marked impact on the assessment of cardiac damage perhaps even more so than the original introduction of the troponins. The afternoon featured three speakers discussing the pro and cons of high-sensitivity C-reactive protein for the assessment of cardiovascular disease. Dr. Jean Grégoire (Institut de cardiologie de Montréal) presented the pro side of the debate reviewing in particular the recent Jupiter trial. Dr. James Brophy (MUHC) presented the con side of the debate in a most entertaining manner. He even had the audience performing stretching exercises! It was left to Dr. Jean Bergeron (CHUL) to provide a balanced view of the two preceding speakers. The last day, Day 4, was primarily dedicated to oral and poster presentations by the residents. A jury consisting of Drs. Jean Dubé (CHUS), Yves Guigère (CHUL), and Joël Girouard (CHUL) had the “difficult” task of awarding prizes to the best oral and to the best poster presentations. The winners this year were Dr. Alexis Blaass (U. de Montréal) for the oral presentation entitled “Characterization of a new LCAT mutation causing familial LCAT deficiency (FLD) and the role of APOE as a modifier gene of the FLD phenotype” and Dr. Adell Elsharif (McMaster U.) for the poster presentation entitled “Method Validation Study to Evaluate the Analytical Performance of the STAT–SITE Meter for the Measurement of Serum Beta-Hydroxybutyrate”. The scientific portion of the conference ended with a most comprehensive presentation on smoking cessation, both clinical approaches and therapeutics by Dr. Joanne Provencher (Hôpital Laval). Dr. Provencher reminded us that smoking cessation by an individual could be achieved with the correct support. The day and the congress ended with a business meeting of the CAMB chaired by the out going president, Dr. Bassam A. Nassar. A new executive was elected: Dr. Elizabeth MacNamara (SMBD-Jewish General Hospital, president), Dr. Yves Guigère (CHUL, vice-president), Dr. Andrew Don-Wauchope (McMaster U. Health Sciences Centre, secretary-treasurer), Dr. Andre Mattman (BCCWHC, councilor), Dr. Brian M. Gilfix (MUHC, councilor), Dr. John Heathcote (Vancouver, councilor), and Dr. Datlily Ooi (Children’s Hospital of Eastern Ontario, councilor), We all look forward to next year’s combined meeting which is again slated to take place in Montreal in October

Report and abstracts of the Joint Annual Congress of the AMBQ-CAMB 2010

The third joint congress of l’Association des Médicins Biochimistes du Québec (AMBQ) and the Canadian Association of Medical Biochemists (CAMB) was held this year from October 19 to 22 in Montreal. The setting was like last year the picturesque Hôtel Place d’Armes, which is situated in the historic Old Montreal district. There were over 60 attendees comprising both Specialists and Medical residents-in-training and representing the breadth of Canada from the Atlantic to the Pacific. The scientific committee composed of Drs. Shaun Eintracht (SMBD-Jewish General Hospital (JGH)), Brian M. Gilfix (McGill University Health Centre (MUHC)), David Blank (MUHC), Elizabeth MacNamara (JGH), and Julie St-Cyr (St. Mary’s Hospital (SMH)) arranged a series of informative and interesting scientific sessions

Severe hyperhomocysteinemia due to cystathionine beta-synthase deficiency, and Factor V Leiden mutation in a patient with recurrent venous thrombosis

Homocysteine is an amino acid that is toxic to vascular endothelial cells, and plasma elevations have been associatedwith venous thromboembolism. Severe hyperhomocysteinemia (>100 μmol/L) may result from mutations in the genescoding for enzymes in the trans-sulfuration or the folate/vitamin B12-dependent re-methylation pathways. Here, wereport the case of a young woman with severe, recurrent thrombo-embolic events associated with severehyperhomocysteinemia (111 μmol/L). We identified a homozygous mutation in the cystathionine β -synthase gene(p.I278T) and the presence of the Factor V Leiden mutation. Family study shows segregation of elevated homocysteinein heterozygous relatives for the mutation in the cystathionine β -synthase gene. Management consisted ofanticoagulation with warfarin and supplementation with folate, vitamin B6 (pyridoxine) and vitamin B12. After twelveyears of follow-up, plasma homocysteine levels remain in the moderate range (~20 μmol/L, reference range 8-12 μmol/L)and no further thromboembolic events were identified

Biochemical analysis of patients with mutations in MTHFD1 and a diagnosis of methylenetetrahydrofolate dehydrogenase 1 deficiency

MTHFD1 is a trifunctional protein containing 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase and 5,10-methylenetetrahydrofolate dehydrogenase activities. It is encoded by MTHFD1 and functions in the cytoplasmic folate cycle where it is involved in de novo purine synthesis, synthesis of thymidylate and remethylation of homocysteine to methionine. Since the first reported case of severe combined immunodeficiency resulting from MTHFD1 mutations, seven additional patients ascertained through molecular analysis have been reported with variable phenotypes, including megaloblastic anemia, atypical hemolytic uremic syndrome, hyperhomocysteinemia, microangiopathy, infections and autoimmune diseases. We determined the level of MTHFD1 expression and dehydrogenase specific activity in cell extracts from cultured fibroblasts of three previously reported patients, as well as a patient with megaloblastic anemia and recurrent infections with compound heterozygous MTHFD1 variants that were predicted to be deleterious. MTHFD1 protein expression determined by Western blotting in fibroblast extracts from three of the patients was markedly decreased compared to expression in wild type cells (between 4.8 and 14.3% of mean control values). MTHFD1 expression in the fourth patient was approximately 44% of mean control values. There was no detectable methylenetetrahydrofolate dehydrogenase specific activity in extracts from any of the four patients. This is the first measurement of MTHFD1 function in MTHFD1 deficient patients and confirms the previous molecular diagnoses

Impact of transfusion of mediastinal shed blood on serum levels of cardiac enzymes

Infusion of shed mediastinal blood using an autotransfusion system is a widely applied technique of blood conservation in cardiac surgery. Serial determinations of serum creatine kinase (CK), its MB isoenzyme (CK-MB), and lactate hydrogenase (LDH) levels have been used to monitor perioperative myocardial injury. We investigated the impact of postoperative autotransfused blood infusion on serum levels of these enzymes. We performed a retrospective analysis of postoperative serum CK, CK-MB, and LDH levels of 300 patients who had elective uncomplicated aortocoronary bypass grafting. Shed mediastinal blood samples from 26 patients were analyzed for CK, CK-MB (enzymatic activity and mass), and LDH levels before infusion. High postoperative serum levels of CK and LDH were observed after infusion of autotransfused blood. Shed mediastinal blood contained extremely high levels of these enzymes, particularly from patients who had internal mammary artery dissection. There was a strong correlation (r = 0.96) between measured CK-MB enzyme activities and those calculated from the CK-MB mass units. Infusion of autotransfused blood containing high concentrations of CK and LDH results in elevated serum levels of these enzymes. Hemolysis, frequently present in shed blood, does not interfere with the routine biochemical assays for CK and CK-MB enzyme activities. Caution should be taken when postoperative cardiac enzyme levels are used to determine myocardial injury after aortocoronary bypass grafting if autotransfusion is used as a method of blood conservation

The novel aminoglycoside, ELX-02, permits CTNSW138X translational read-through and restores lysosomal cystine efflux in cystinosis.

BACKGROUND:Cystinosis is a rare disorder caused by recessive mutations of the CTNS gene. Current therapy decreases cystine accumulation, thus slowing organ deterioration without reversing renal Fanconi syndrome or preventing eventual need for a kidney transplant.15-20% of cystinosis patients harbour at least one nonsense mutation in CTNS, leading to premature end of translation of the transcript. Aminoglycosides have been shown to permit translational read-through but have high toxicity level, especially in the kidney and inner ear. ELX-02, a modified aminoglycoside, retains it read-through ability without the toxicity. METHODS AND FINDINGS:We ascertained the toxicity of ELX-02 in cells and in mice as well as the effect of ELX-02 on translational read-through of nonsense mutations in cystinotic mice and human cells. ELX-02 was not toxic in vitro or in vivo, and permitted read-through of nonsense mutations in cystinotic mice and human cells. CONCLUSIONS:ELX-02 has translational read-through activity and produces a functional CTNS protein, as evidenced by reduced cystine accumulation. This reduction is comparable to cysteamine treatment. ELX-02 accumulates in the kidney but neither cytotoxicity nor nephrotoxicity was observed