Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D). We investigated the associations of these previously reported common variants in these genes with insulin resistance in overweight children from Romania and Moldova. Methods Six single nucleotide polymorphisms (SNPs), IGF1 (rs35767), IRS1 (rs2943634), GCKR (rs780094), PPARG (rs1801282), GCK1 (rs1799884) and KCTD15 (rs29941), were genotyped in 100 overweight children along with clinical and metabolic parameters. Homeostatic model assessment of insulin resistance (HOMA-IR) above 3.4 (defining insulin resistance) was used as the outcome. Results Children differed in insulin resistance status despite having similar body mass index (BMI) standard deviation scores (SDS) (World Health Organization, [WHO] reference). The identified predictors for altered insulin metabolism were higher cholesterol levels, higher diastolic blood pressure and higher waist-to-hip-ratio (as a marker for increased abdominal fat). None of the SNPs showed significant association with increase in the risk for insulin resistance in children (p range=0.478–0.724; odds ratio [OR] range=1.924–4.842); however, the risk allele in GCKR (rs780094, p=0.06, OR=6.871) demonstrated near statistical significance. Conclusions The interrogated risk alleles did not show any significant association with insulin resistance in children in our cohort; however, the GCKR (rs780094) might be a viable candidate in larger cohorts. The lack of replication of the proposed association may point to differences in linkage disequilibrium or effect modifiers across studies.

The paper reports on monitoring methylmalonic aciduria (MMA)-specific and non-specific metabolites via NMR urinomics. Five patients have been monitored over periods of time; things involved were diet, medication and occasional episodes of failing to comply with prescribed diets. An extended dataset of targeted metabolites is presented, and correlations with the type of MMA are underlined. A survey of previous NMR studies on MMA is also presented.

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Background: Congenital Disorders of Glycosylation (CDG) are a group of inherited metabolic disorders caused by the defect in various steps in the biosynthesis of glycoproteins and other glycoconjugates. Material and methods: 40 patients under clinical suspicions for CDG at the Institute of Mother and Child were examined by isoelectric focusing of transferrin (IEFT) in collaboration with RadboudUMC, Netherlands and U.S.A. The spectrum of clinical presentations of these patients was multisystem damage, predominantly neurological manifestations. Results: Most of the patients (55%) had early neurological manifestations from the birth, such as hypotonia, psychomotor disability, cerebral MRI abnormalities, seizures (25%), cutis laxa (17.5%), total alopecia (2.5%), abnormal fat pads (2.5%), myopia (7.5%), nystagmus (5%), strabismus (2.5%), stroke-like episodes (2.5.%), ataxia (7.5%), abnormal coagulation (10%), hepatomegaly (35%) and liver cirrhosis (2.5%). Serum samples analyzed by IEFT showed the results: 37 normal, 2 questionable and 1 abnormal patterns. Two samples questionable belongs to the patients with Galactosemia and Fructosemia, which give the false-positive results. The last positive sample is performed additionally for glycomics profiling. In some cases, with IEFT negative profile was performed genetic test and were diagnosed other diseases, mimicking CDG, such as: NARP syndrome, late diagnosed PKU, GSD, Manosidoses, Prader-Willi Syndrome and chromosomal aberrations. Conclusions: The CDG is a rare metabolic disease with multisystem impairment and variety of symptoms which determine overlapping of phenotype with other genetic disorders. The process of diagnosis is very complex and can take several years.