Morquio Syndrome is a rare, inherited metabolic disorder affecting the body’s ability to break down complex sugar molecules called glycosaminoglycans (GAGs). It involves the accumulation of keratan sulfate within cells and tissues, leading to physical challenges, primarily affecting the skeleton and other organ systems. The risk of inheriting or passing on Morquio Syndrome is rooted in specific genetic changes.
Genetic Foundation of Morquio Syndrome
Morquio Syndrome arises from alterations in specific genes, leading to a deficiency in enzymes responsible for breaking down keratan sulfate. There are two primary types of Morquio Syndrome, distinguished by the gene affected and the enzyme involved. Morquio A, the more common form, is caused by mutations in the GALNS gene, which provides instructions for producing the N-acetylgalactosamine-6-sulfatase enzyme.
Morquio B, the less common type, results from mutations in the GLB1 gene, responsible for the beta-galactosidase enzyme. In both types, the enzyme deficiency prevents proper keratan sulfate degradation, leading to its accumulation within lysosomes inside cells. This abnormal GAG accumulation causes progressive damage to various tissues and organs, particularly bones, cartilage, and other connective tissues.
Inheritance Pattern and Family Risk
Morquio Syndrome follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of a mutated gene, one from each parent, to develop the condition. If a person inherits only one copy of the mutated gene and one normal copy, they are considered a “carrier” of the condition. Carriers typically do not exhibit symptoms because their single functional gene copy produces enough of the necessary enzyme to prevent significant keratan sulfate buildup.
When both parents are carriers, their children face specific probabilities with each pregnancy. There is a 25% chance their child will inherit two mutated copies of the gene and develop Morquio Syndrome. There is a 50% chance their child will inherit one mutated and one normal copy, becoming a carrier. Finally, there is a 25% chance the child will inherit two normal copies, being unaffected and not a carrier. These probabilities remain the same for every pregnancy.
Assessing Risk Through Genetic Counseling and Testing
For individuals and families, several methods exist to assess the risk of Morquio Syndrome. Genetic counseling is often recommended for those with a family history of the disorder or other related metabolic conditions. A genetic counselor can explain inheritance patterns, discuss potential risks, and help families understand their options.
Carrier screening tests can identify if an individual carries a mutation in the GALNS or GLB1 gene. These tests typically involve analyzing a blood or saliva sample for genetic alterations.
For at-risk pregnancies, prenatal diagnosis methods such as amniocentesis or chorionic villus sampling (CVS) can determine if the fetus is affected. These procedures involve collecting cells from amniotic fluid or placenta for genetic and enzyme activity testing. Newborn screening programs are emerging in some regions, identifying infants with Morquio Syndrome shortly after birth for earlier intervention.