Homozygous
By definition, the forms of MODY are autosomal dominant, requiring only one abnormal gene to produce the disease; the severity of the disease is moderated by the presence of a second, normal allele which presumably functions normally. However, conditions involving people carrying two abnormal alleles have been identified. Unsurprisingly, combined (homozygous) defects of these genes are much rarer and much more severe in their effects. MODY2: Homozygous glucokinase deficiency causes severe congenital insulin deficiency resulting in persistent neonatal diabetes mellitus. About 6 cases have been reported worldwide. All have required insulin treatment from shortly after birth. The condition does not seem to improve with age. MODY4: Homozygous IPF1 results in failure of the pancreas to form. Congenital absence of the pancreas, termed pancreatic agenesis, involves deficiency of both endocrine and exocrine functions of the pancreas.Homozygous mutations in the other forms have not yet been described. Those mutations for which a homozygous form has not been described may be extremely rare, may result in clinical problems not yet recognized as connected to the monogenic disorder, or may be lethal for a fetus and not result in a viable child. Pathophysiology
The recognised forms of MODY are all due to ineffective insulin production or release by pancreatic beta cells. Several of the defects are mutations of transcription factor genes. One form is due to mutations of the glucokinase gene. For each form of MODY, multiple specific mutations involving different amino acid substitutions have been discovered.
Liver adenoma or hepatocellular carcinoma in MODY type 3
Renal cysts, rudimentary or bicornuate uterus, vaginal aplasia, absence of the vas deferens, epidymal cysts in MODY type 5The diagnosis of MODY is confirmed by specific gene testing available through commercial laboratories. Classification
Common or well-established forms of MODY (1% of MODY or greater) - HNF1A-(MODY3), HNF4A-(MODY1) and GCK-(MODY2), HNF1B-(MODY5), ABCC8-(MODY12), KCNJ11-(MODY13), INS-(MODY10)
Rare forms of MODY (Few families described but reasonable generic evidence for causing MODY) - NEUROD1-(MODY6), IPF1/PDX1-(MODY4), CEL-(MODY8), WSF1 and RFX6
Genes reported as causal for MODY but evidence not compelling - BLK-(MODY11), PAX4-(MODY9) and KLF11-(MODY7), APPL1-(MODY14), NKX6-1

Treatment
In some forms of MODY, standard treatment is appropriate, though exceptions occur:

In MODY2, oral agents are relatively ineffective, however most patients are managed conservatively through diet and exercise. In MODY1 and MODY3, sulfonylureas are usually very effective, delaying the need for insulin treatment. Sulfonylureas are effective in the KATP channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested that the reduced clearance of sulfonylureas stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently to the mouse model and that there was no consistent decrease in the clearance of sulfonylureas in randomly selected HNF1A-MODY and HNF4A-MODY patients.Chronic hyperglycemia due to any cause can eventually cause blood vessel damage and the microvascular complications of diabetes.