SNP Shot: Genomic Insights

Permanent neonatal diabetes mellitus (PNDM) is a form of diabetes diagnosed within the first six months of life and lasting indefinitely. It is defined by high blood glucose (hyperglycemia) due to a deficiency in insulin, the hormone that regulates the movement of glucose (sugar) from the bloodstream into cells for energy use.

Babies with PNDM often experience restricted growth before birth (intrauterine growth retardation). After birth, they exhibit hyperglycemia, dehydration (excessive fluid loss), and struggle to gain weight and grow at the expected pace (failure to thrive).

Some individuals with PNDM also present with neurological issues such as developmental delays and recurring seizures (epilepsy). The presence of developmental delay, epilepsy, and neonatal diabetes is referred to as DEND syndrome. A similar condition, intermediate DEND syndrome, involves milder developmental delays but without epilepsy.

A small subset of individuals with PNDM have an underdeveloped pancreas. The pancreas produces both digestive enzymes and hormones like insulin. As a result, these individuals may experience digestive difficulties such as fatty stools and difficulty absorbing fat-soluble vitamins.

Inheritance:

The inheritance pattern of PNDM varies depending on the causative gene. When caused by mutations in the KCNJ11 or INS gene, it follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is enough to cause the condition. Approximately 90% of these cases arise from new, spontaneous mutations in the gene, occurring in individuals with no family history of the disorder. The remaining cases involve inheritance of the mutation from an affected parent. PNDM caused by ABCC8 gene mutations can be inherited in either an autosomal dominant or autosomal recessive manner. Autosomal recessive inheritance requires both copies of the gene in each cell to be mutated. In this case, the parents of an affected individual each carry one copy of the mutated gene but usually do not exhibit any symptoms. Less frequently, PNDM is caused by mutations in other genes, and these cases also typically follow an autosomal recessive inheritance pattern.