SNP Shot: Genomic Insights

Nephrogenic diabetes insipidus (NDI) is a condition affecting the body's ability to regulate fluid balance. Normally, fluid intake is balanced by fluid excretion through urine. However, individuals with NDI produce excessive amounts of urine (polyuria), leading to extreme thirst (polydipsia). Insufficient water intake, particularly in hot environments or during illness, can quickly result in dehydration.

NDI can be either acquired or inherited. The acquired form can develop at any point in life and is often triggered by specific medications or chronic illnesses. The hereditary form, caused by genetic changes, typically manifests within the first few months of life.

Infants with hereditary NDI may exhibit poor feeding, failure to gain weight and grow as expected (failure to thrive), irritability, fever, diarrhea, and vomiting. Repeated dehydration episodes can hinder growth and development. If left unmanaged, the condition can eventually damage the bladder and kidneys, leading to pain, infections, and kidney failure. With appropriate treatment, most individuals with NDI experience few complications and have a normal lifespan.

It's important to distinguish nephrogenic diabetes insipidus from diabetes mellitus, a far more prevalent condition. Diabetes mellitus is characterized by elevated blood sugar (glucose) levels resulting from insulin deficiency or insulin resistance. While sharing some superficial similarities, NDI and diabetes mellitus are distinct disorders with different underlying causes.

Inheritance:

When NDI is caused by mutations in the AVPR2 gene, it follows an X-linked recessive inheritance pattern. The AVPR2 gene resides on the X chromosome, one of the two sex chromosomes. Males, having only one X chromosome, develop the condition with just one altered copy of the gene in each cell. Females, possessing two X chromosomes, typically require mutations in both gene copies to manifest the disorder. However, some females carrying a single mutated AVPR2 gene may exhibit symptoms of NDI, such as polyuria and polydipsia. A key feature of X-linked inheritance is that fathers cannot transmit X-linked traits to their sons.

When NDI results from mutations in the AQP2 gene, it can be inherited in either an autosomal recessive or, less frequently, an autosomal dominant manner. In autosomal recessive inheritance, both copies of the gene in each cell must be mutated. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but usually do not display signs or symptoms of the condition. In autosomal dominant inheritance, only one mutated copy of the AQP2 gene in each cell is sufficient to cause the disorder.