SNP Shot: Genomic Insights

Maturity-onset diabetes of the young (MODY) encompasses a group of related conditions characterized by elevated blood glucose levels, also known as high blood sugar. These forms of diabetes typically manifest before the age of 30, although they can sometimes appear later in life. The underlying cause of high blood sugar in MODY is a reduction in insulin production. Insulin, a hormone produced by the pancreas, plays a crucial role in regulating blood glucose by enabling glucose (a type of sugar) to move from the blood into cells for energy.

The different types of MODY are classified according to their specific genetic mutations. HNF1A-MODY (also called MODY3) is the most common type, accounting for 50% to 70% of cases. GCK-MODY (MODY2) is the next most prevalent, representing 30% to 50% of cases. Less common types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), each contributing to 5% to 10% of cases. There are at least ten other identified types, but these are quite rare.

HNF1A-MODY and HNF4A-MODY share similar signs and symptoms that develop gradually. These early symptoms, resulting from high blood glucose, can include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurring skin infections. Over time, sustained high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the retina, the light-sensitive tissue at the back of the eye, leads to diabetic retinopathy, potentially causing vision loss and blindness. Kidney damage (diabetic nephropathy) can progress to kidney failure and end-stage renal disease (ESRD). While these two MODY types are similar, certain characteristics distinguish them. For example, infants with HNF4A-MODY often have a higher-than-average birth weight or abnormally low blood glucose levels at birth, even if other symptoms don't appear until later. Individuals with HNF1A-MODY have an increased risk of developing noncancerous liver tumors called hepatocellular adenomas.

GCK-MODY is a relatively mild form of the condition. Individuals with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, they often experience no related symptoms, and diabetes-related complications are extremely rare.

RCAD involves a combination of diabetes and kidney or urinary tract abnormalities (distinct from those caused by high blood glucose), typically fluid-filled cysts in the kidneys. The signs and symptoms vary considerably, even within the same family, and not everyone with RCAD exhibits both diabetes and kidney problems. Affected individuals may also have other unrelated features, such as pancreas or liver abnormalities, or gout, a type of arthritis.

Inheritance:

MODY follows an autosomal dominant inheritance pattern. This means that having only one copy of the mutated gene in each cell is sufficient to cause the condition. In most instances, an affected person inherits the mutation from a parent who also has MODY. In other instances, the mutation arises spontaneously in the gene, occurring in individuals with no family history of the condition.