Monitoring Methylmalonic Aciduria by NMR Urinomics.

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.

Gaucher disease type 1: the first experience of enzyme replacement therapy in pediatric practice in Moldova - case report.

We report on a case of a little girl patient diagnosed with Gaucher disease (GD) type 1 in her early childhood and our first experience with enzyme replacement therapy (ERT). She was first diagnosed accidentally with enlarged spleen during a pediatric examination when she was three years old, but the family ignored investigations; she was hospitalized for diagnosis at six years old. The GD was confirmed based on: clinical manifestations of left abdominal flank pain, multiple bruising, general weakness, bone pain, low appetite, failure to thrive <5th percentile, minor hepato- and severe splenomegaly, enlarged submaxillary lymph nodes, associated by anemia with normal platelets; low activity of beta-Glucosidase, two found mutations in GBA gene, Gaucher cells in bone marrow. The ERT was initiated with Imiglucerase (54 UI/kg/2 wks) two years later after diagnosis, avoiding the splenectomy. Subsequently, the platelets showed the first a promising result, gradually increasing their number every 2 weeks and maintaining it in good parameters till the reported moment (2.5 yrs from the start). The hemoglobin level was appreciated within normal ranges 3 months after ERT start and stabilized completely after 6 months. On the other hand, the red blood count normalized within 20 months of applied therapy. The Lyso-GL-1 decreased by 30% after three months of therapy, no antibodies to Imiglucerase were found. The initial spleen volume (1178.19 cm3) decreased by almost 60% in 6 months of ERT, reaching absolutely normal dimensions after 9 months. The ERT with Imiglucerase was tolerated very well by the patient, showing a clear improvement of clinical symptoms after 4-6 months of therapy, hematological picture and splenomegaly solving. Even if the little patient had to come every 2 weeks for infusion, her quality of life improved a lot, being a totally happy child, going to school and having friends. The ERT should be initiated immediately after diagnosis to prevent the multisystem complications.

No clinical utility of common polymorphisms in IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 genes previously associated with insulin resistance in overweight children from Romania and Moldova.

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.