Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.

We evaluated 132 galactosemia patients for the Q188R (glutamine-188 to arginine) mutation in the human galactose-1-phosphate uridyltransferase (GALT) gene and for GALT activity in their hemolysates by a sensitive radioisotopic method. In those without any detectable GALT activity (GG), the Q 188R mutation constituted 67% of the alleles. In patients with detectable GALT activity (GV), only 16% of the alleles were accounted for by Q188R. In all patients who were homozygous for the Q188R mutation, no erythrocyte GALT activity could be demonstrated. There was an extensive variation in the amount of detectable GALT activity ranging from 0.1% to 5% of the normal values among the GV patients. There was a difference in the frequency of Q188R mutation in the GALT alleles among patients belonging to different racial and ethnic groups. In Caucasian and Hispanic patients, the frequency was not far different (64% and 58%, respectively). On the other hand, only 12% of the GALT alleles with Q188R were found in African-American patients.

Cobalamin (Vitamin B12) plays an essential role both in the conversion of methylmalonyl-CoA to succinylCoA and in the synthesis of methionine (Met) from homocysteine (Hcy). Elevations of total homocysteine (tHcy), Met, methylmalonic acid (MMA), and 2-methylcitric acid (2MCA) are indicative of disorders in these related pathways, and can clinically present as methylmalonic acidemia, cobalamin defects or deficiency, propionic acidemia, homocystinuria, and hypermethioninemia. We have developed a fast, sensitive, and simple method for the simultaneous detection of plasma tHcy, MMA, Met, and 2MCA using liquid chromatography mass spectrometry (LC/MS/MS). All analytes were directly determined without the need of derivatization. Both positive and negative modes were used to achieve the best sensitivity and specificity. The two stereo isomers of 2MCA (2S, 3S) and (2R, 3S) were successfully separated and were designated as 2MCA1 and 2MCA2. The assays were linear up to a concentration of 800 mMol/l for tHcy, 2,000 mMol/l for Met, 80 mMol/l for MMA, 40 mMol/l for 2MCA1, and 40 mMol/l for 2MCA2 (80 mMol/l for total 2MCA), respectively. The recovery was between 84.42 % and 120.05 %.The intra-assay coefficient of variations (CVs) ranged from 2.1 % to 6.9 % (n = 20), and the inter-assay CVs ranged from 2.7 % to 11.6 % (n = 20). Reference intervals were established and verified (n = 125). A total of 15 patients with variable disorders in related pathway were successfully confirmed. The assay can be performed either in diagnostic laboratories or as second-tier, follow-up test in newborn screening laboratories.A fast, sensitive, and simple LC/MS/MS method was developed successfully for the simultaneous detection of plasma total homocysteine, methylmalonic acid, methionine, and 2-methylcitric acid for diagnosis of disorders in related pathways.

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