Dawn/Kathy //All re:elevated B-12

[Guest guest]

Hey Dawn-

I just got this e-mail from one of Maddies Metabolics docs. Thought you might be interested. I'm going to call her ped. on Monday to schedule these specific labs. I'll let you know if I get any more information. This just goes to show that our "gut instinct", "ruthless perseverance" and of course unlimited resources on the web pay off. Her docs were ready to dismiss the whole b-12 issue until I shared some of the info. you all shared with me, and because I kept bringing up the optic nerve atrophy related to b-12 deficiency they researched it further. (This of coarse was after 3 phone conversations, in one of which the doc told me my medical knowledge is "minute" as well as 2 e-mail correspondences) Anyhow- just thought I'd share! Hope everyone has a great weekend.

Holly

Holly,

I put Maddie's information and lab test results out on the wordwide metabolic disease list-serv. Most of the replies said that elevated B12 is a commonly seen event in patients with mitochondrial disease and is of no therapeutic significance. A few wondered if you could be right and made suggestions about who might be willing to look further. Several recommended further testing, which I was planning to offer you at the July 26th visit. So if you are interested in getting further testing done before your next visit, the tests they recommended are:

hemogram (hemoglobin, hematocrit, and red blood cell indices)

methylmalonic acid level

homocysteine level

(current) lactate level

There seems to be a consensus that we don't understand enough about these conditions! But I'm sure you already know that...

-- Root

Root, MDClinical GeneticistDepartment of PediatricsUniversity of New Mexico

[Guest guest]

Holly,

Thanks for passing along this info! I am glad that they are

checking things out for you. This also helps me to further beleive

that my undiagnosed daughter Molly has mito for sure. Her b12 levels

are actually higher than 's! Keep us updated as things

progress.

thanks, dawn

[Guest guest]

Hi Holly:

Thank you for me also! No one could give me any information as to why my sons' B-12 was sky high!

Can I Fw this to their p-doc ?

Cindy-GA

Re: Dawn/Kathy //All re:elevated B-12

Holly, Thanks for passing along this info! I am glad that they are checking things out for you. This also helps me to further beleive that my undiagnosed daughter Molly has mito for sure. Her b12 levels are actually higher than 's! Keep us updated as things progress. thanks, dawn

[Guest guest]

Re: Dawn/Kathy //All re:elevated B-12

Holly,I am glad that your daughter's doctor is investigating this further.The test that were ordered sounded reasonable, but I wish that theywould have also investigated glutathione.Here is some more info from a "reputable" website and another articlethat you might find interesting.http://wwwthorne.com/pdf/journal/2-6/coenzymeb12.pdfThe Coenzyme Forms of Vitamin B12: Toward an Understanding of theirTherapeutic PotentialFrom the Kent State University faculty websiteBioinorganic and Medicinal ChemistryWe are interested in vitamin B12 derivatives and B12-dependent enzymereactions (see Figure). A deficiency in vitamin B12 can lead to anemia("pernicious anemia") and/or neurological disorders. Of the 15 or sovitamin B12-dependent enzyme reactions known, two of these reactions,involving methionine synthase and methylmalonyl-CoA mutase, occur inhumans. In the former reaction, the vitamin B12 derivativemethylcobalamin is an intermediate in the methylation of homocysteineby methyl-tetrahydrofolate. A current "hot topic" in the medicalliterature is the recently demonstrated relationship between highserum levels of homocysteine and a greatly increased risk of strokesor heart attacks. In addition, there is increasing evidence thatindividuals with high serum levels of homocysteine are more likely todevelop neurological disorders. We have recently begun to collaboratewith Dr. McCaddon and his research team in Wales, who areinterested in the relationship between aberrant B12 metabolism andAlzheimer's disease. As part of this work, we have developed a new,simple procedure to synthesize the vitamin B12 derivativeglutathionylcobalamin, and are currently investigating its propertiesunder biological conditions. Glutathionylcobalamin is a naturallyoccurring vitamin B12 derivative, and could very well be a precursorto both the B12 coenzymes, methylcobalamin and5 & #8242;-deoxyadenosylcobalamin. Structure of vitamin B12 and its derivatives X=CN: cyanocobalamin (vitamin B12) X=CH3: methylcobalamin X=5 & #8242;-deoxyadenosyl: adenosylcobalamin X=glutathione: glutathionylcobalaminOther areas of interest include the synthesis and properties ofvitamin B12 bioconjugates. Recently we have prepared the first vitaminB12 bioconjugate which could potentially be an active, orallyadministered pharmaceutical for the treatment of diabetes. The abilityof vitamins to act as drug carriers (or vectors) for transportingorally administered pharmaceuticals to cells has been recognised forsome time. Only small, neutral, water-soluble molecules can passacross biological membranes to any degree by passive diffusion. Due tothe large size of vitamins, these important biomolecules are thereforetypically associated with active transport mechanisms for absorptionand cellular uptake. This is especially important for vitamin B12,given the very small amounts that are present in most foods. Utilizingvitamin B12 bioconjugates for the transportation of drugs has beenshown to have applications in the uptake of both peptides and proteinsadministered orally. Cobalamin-diethylene-triaminepenta-acetate(DTPA)-metal conjugates have been identified as potential diagnosticimaging agents for tumors (111In, 99Tc) and MRI (57Gd)contrast-enhancing agents. Fluorescent B12 conjugates also show muchpromise in diagnostic imaging. Importantly, thechloroambucil-cobalamin bioconjugate has shown considerable potentialfor the treatment of leukemia. In addition to synthesizing B12bioconjugates, studies designed at probing the stability of thecomplexes under physiological conditions will also be carried out.Collaborations will also be established with other groups to examinethe in vitro and/or in vivo properties of the more promising complexes.We have recently embarked upon a completely new area of research forus: vanadium chemistry. The importance of vanadium in biology firstattracted attention through the work of Henze and co-workers,who discovered high concentrations of vanadium(III) in the blood cellsof sea squirts. Ascidians of the suborder Phlebobranchia are smallmarine animals that sequester vanadium(V) from seawater and reduce itto vanadium(III). How or why these creatures accumulate this metal ionis unknown. In addition, the chemistry of vanadium(III) itself,especially in aqueous systems, is poorly defined compared with that ofvanadium in the more stable oxidation states of +4 and +5. Our studiesof vanadium(III) complexes have commenced with simple ligands such asamino acids, or ligands which model amino acids.Selected PublicationsBrasch, N.E., * Hamilton, I.G.; Krenske, E.H.: Wild, S.B.* LigandExchange on Phosphenium Ions: Reversible Exchange between Free andCoordinated Alkynes in Phosphirenium Salts. Organomet. 2004, 23, 299.Bernado, P.H.; Brasch, N.; Chai, C.L.L.; Waring, P.* A Novel RedoxMechanism for the Glutathione-dependent Reversible Updatke of a FungalToxin in Cells. J.Biol. Chem. 2003, 278, 46549.Brodie, S.F.; Cregan, A.G.; van Eldik, R.; Brasch, N.E.* The ReactionBetween Methylcobalamin and Cyanide Revisited. Inorg. Chim. Acta.2003, 348, 221.PatentsBrasch, N.E.;* Xia, L. Method of Synthesis of & #946;-thiolato CobalaminNucleoside Compounds, U.S. Patent Application 20040054128, 2004.Last Updated: 21 May 2004