An infant with combination gene mutations for Monogenic Diabetes of Youth (MODY) 2 and 4, presenting with Diabetes Mellitus Requiring Insulin (DMRI) at 8 months of age.

Monogenic Diabetes of Youth (MODY) is an autosomal dominant form of diabetes. [Fajans SS, et al. NEJM 2001: 345: 971-980.] There are at least six different types of MODY, all of which involve a loss of function gene mutation that results in diminished insulin production. MODY2 results from a mutation in the glucokinase gene (GCK), which decreases enzyme activity. MODY4 results from a mutation in the insulin promoter factor-1 (IPF-1) gene, a transcription factor which regulates the transcription of insulin. [Sperling M, et al. NEJM 2006: 355: 507-510.] TJ presented at 8 months of age with diabetes mellitus requiring insulin (DMRI) with negative islet autoantibodies. She had a prolonged honeymoon period, as evidenced by her insulin requirement of 0.5 units/kg/day at three years of age. Genetic testing showed combination MODY2 (c.1019+18G >A) and MODY4 (c.226G>A) gene mutations. The father was homozygous for MODY2 and the mother was heterozygous for MODY4. [Athena Diagnostics Evaluations "2007 # 839 - Monogenic Diabetes (MODY) Evaluation for the patient, the patient's father, and the patient's mother] Neither parent had diabetes mellitus. The clinical course and negative islet autoantibodies support that the combination of benign MODY2 and MODY4 gene mutations in the parents resulted in DMRI in TJ.

T-regulatory/T-helper 17: promiscuous signals and fear of commitment.

The insight gained recently on the differentiation of naive CD4 T cells challenges the dogma that expression of canonical transcription factors and production of signature cytokines portray a commitment to a specific lineage and a point of no return. For almost two decades now, the belief has been that naive CD4 T cells, under the guidance of environmental signals, follow a one-way road to evolve as Th1, Th2, Th17 or regulatory T cells (Tregs). The current paper, however, demonstrates a crosstalk between signals and identifies transitory T-cell states whereby a differentiating CD4(+) T cell will express a mixed Th17 and Treg phenotype. Moreover, they were able to successfully reprogram terminally differentiated Tregs into Th17 cells, suggesting that redifferentiation could occur and provides an environmental plasticity to readjust immunity. This suggests that T-cell differentiation does not necessarily follow a one-way road, but that traffic may flow in both directions.