SNP Shot: Genomic Insights

Congenital dyserythropoietic anemia (CDA) is a genetic blood disorder that impairs the proper development of red blood cells. As a type of anemia, CDA results in a deficiency of red blood cells. This deficiency hinders the blood's ability to deliver sufficient oxygen to the body's tissues, leading to symptoms like fatigue, weakness, and pale skin, along with potential further health issues.

CDA is classified into three primary types: type I, type II, and type III. These types are distinguished by their unique genetic origins and slightly differing, yet related, signs and symptoms.

CDA type I is marked by anemia ranging from moderate to severe. Diagnosis typically occurs during childhood or adolescence, though it can sometimes be identified prenatally. Common features include jaundice (yellowing of the skin and eyes) and hepatosplenomegaly (enlarged liver and spleen). A key characteristic is excessive iron absorption, leading to iron accumulation that can damage various tissues and organs. This iron overload can specifically cause arrhythmia (irregular heartbeat), congestive heart failure, diabetes, and cirrhosis (chronic liver disease). Infrequently, individuals with CDA type I may be born with skeletal abnormalities, primarily affecting the fingers and/or toes.

CDA type II can manifest with anemia varying in severity from mild to severe. Most individuals exhibit jaundice, hepatosplenomegaly, and the development of gallstones in the gallbladder. This type is commonly diagnosed during adolescence or early adulthood. An abnormal buildup of iron generally begins after age 20, potentially resulting in complications like heart disease, diabetes, and cirrhosis.

CDA type III generally presents with milder symptoms compared to the other types. Hepatomegaly and splenomegaly are usually absent, and iron overload is uncommon. In adulthood, retinal abnormalities can develop, causing vision impairment. Some individuals with CDA type III may also develop monoclonal gammopathy, a blood disorder that can progress to multiple myeloma (a type of white blood cell cancer).

Besides the major types, other less common CDA variants have been identified. As research progresses and the genetic causes of these variants are determined, some may be reclassified and grouped with the existing three main types.

Inheritance:

The way CDA is inherited depends on the specific type. CDA types I and II follow an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. The parents, each carrying one copy of the mutated gene, are typically asymptomatic carriers. CDA type III, in certain families, demonstrates an autosomal dominant inheritance pattern. In this pattern, only one copy of the altered gene is needed to cause the disorder. Affected individuals in these families often have an affected parent and other affected relatives.