Urinary methylmalonic acid and cobalamin deficiency in the elderly

Ajay Anand

doi:10.1016/S0002-9343(99)80356-8

$CORRESPONDENCE URINARY METHYLMALONlC ACID AND COBALAMIN E;WX;CY IN THE To the Editor: The study by Drs. Norman and Morrison made very interesting and informat.ive reading.â The high prevalence and availability of therapy for cobalamin deficiency in the elderly make any noninvasive diagnostic index valuable. In this context, I would like to draw your attention to some additional data on this subject. and coworkersZ Yamauchi studied the relation of urinary methylmalonic acid (MMA) excretion and Vit,amin B,, deficiency. They found that patients with neurologic disturbances excreted larger amounts of MMA than those without neurologic disorders. They also concluded that MMA could be a useful adjunct to distinguish megaloblastic anemia from myelodysplasia with niegaloblastosis. As 2% of the general population are carriers of inherited methylmalonic acidemia, Rasmussen and Nathanâ examined the urinary excretion of MMA in patients with methylmalonic acidemia. They found urinary MMA levels to range from 1.18 to 2.48 mm01 per mol of creatinine (reference range 0.58 to 3.56). This reveals that het,erozygotes for inherited methylmalonic acidemia would not give false-positive results for cobalamin deficiency, and hence testing for urinary MMA remains useful in this subgroup. Finally, Rasmussen1 has described the use of another method for the measurement of urinary MMA, anion exchange extraction using formate and formic acid. This technique was found to be both reliable and convenient for the evaluation of cobalamin de& criency, particularly in patients with normal or moderately re514 May 1995 The American Journal duced serum cobalamin levels. The above data, in conjunction with the authorsâ study,â promise to attenuate an important treatable cause of permanent neurologic disability in the elderly. Ajay Anand, MD Division of Hematology and Oncology New England Deaconess Hospital 1. Norman EJ, Morrison JA. Screening elderly pattents for cobalamin (Vitamin 13,~) deficiency using the urinary methylmalonic acid assay by gas chromatography mass spectrometry. Am J Med. 1993;94:58%594. 2. Yamaucht H, Omine M, Tsukamoto N, et al. Urinary methylmalonic acrd excretion and clrnical features in megaloblastic anemia due to Vitamin B!, deficiency. (Japanese). Jon J Chn Hematol. 1989:30:835-839. 3. Rasmussen K. Nathan E. The clinrcal evaluation of cobalamin deflclency by determlnatron of methylmafonic acid in serum or urine IS not invalldated by the presence of heterozygous methylmalonic acldemra. J Cl/n Chem Clin Biochem. 1990;28:419-421. 4. Rasmussen K. Solrdphase sample extraction for rapid determinatton of methylmalonic acrd in serum and urine by a stable-isotope-drlutron method. Urn hem. 1989;35:260-264. Manuscript submItted June 23, 1993 and accepted July 6, 1993. MORE ON HDL SUBFRACTIONS To the Editor: I have read with interest the review on the HDL subfractions by Silverman et al. â Essentially, the article deals with t,he two fundamental subclasses of HDL: HDLZ (density 1.063 to 1.125 g/mL) and HDL3(dl.l25tol210g/mL).Two other subclasses are frequently referred to in the review: Lp(A-I with A-II) and Lp(A-I without AII), based on the presence or absence of apoA-II in the HDL particle; both types occur within the HDL2 and HDL3 density ranges. The authors also mention a number of isolation methodologies other than ultracentrifugation and their disadvantages. One major Volume 98 disadvantage is the alteration of the lipoprotein particle, so that the related classification of HDL may not reflect the physiologic one.â Quite appropriately, they state that âMeasuring subfractions. . . may provide information not, only about atherosclerotic risk but also about the underlying physiologic mechanisms responsible for that risk.ââ A novel technique (isotachophoresis) resolves HDL in at least six subpopulations, which differ for lipid and apolipoprotein composition as well as for their affinity of binding to the cell-surface HDL receptors.â Indeed, the same apolipoprotein contained in different HDL particles assumes different conformations which profoundly affect its function(s).â This consideration leads us to one aspect-function-dealt with in the first part of the review. The range of functions exerted by apolipoproteins is wider than appearing from Table I.â Among these functions, of clinical relevance can be considered the process of repair and nerve regeneration3 and the stimulated release of placental lactogen hormone.â Another property of HDL apolipoproteins is interaction with thyroid hormones (T4, T3) via specific and medium affinity sites (one per molecule). At least for apoA-I and apoE, the two apos studied in greater detail, the respective thyroid hormone binding domain is located in the exon-3 coded region, as opposed to the exon-4 coded lipid binding domain.âj,7 As a result of this interaction, circulating HDL are the major lipoprotein carrier for thyroid hormones. For instance, they carry 2% to 4% of total plasma T4 versus about 0.2% carried by lowdensity lipoproteins (LDL) and 0.03% by very low-density lipoproteins (VLDL).N The LDLT4 complex is internalized by LDL-receptor competent human fibroblasts, indicating that LDL delivers to of Medicineâ$

Urinary methylmalonic acid and cobalamin deficiency in the elderly

Anand, Ajay

Follow The American Journal of Medicine , Volume 98 (5) Elsevier – May 1, 1995