Morquio syndrome, also known as mucopolysaccharidosis type IV (MPS IV), is a rare, progressive genetic disorder. It primarily affects bone and cartilage development, impacting multiple bodily systems. While children appear healthy at birth, symptoms typically emerge between one and three years of age. This condition belongs to a larger group of disorders where the body cannot properly break down certain sugar molecules.
The Genetic Foundation of Risk
Morquio syndrome is an autosomal recessive disorder, meaning a person must inherit two altered gene copies, one from each parent, to develop the condition. These gene mutations prevent the body from producing sufficient enzymes necessary for breaking down complex sugar chains called glycosaminoglycans (GAGs). In Morquio syndrome, GAGs like keratan sulfate and chondroitin-6-sulfate accumulate in various tissues.
There are two types of Morquio syndrome, each linked to a different gene. Morquio A is caused by mutations in the GALNS gene, leading to a deficiency in the N-acetylgalactosamine-6-sulfatase enzyme. Morquio B results from mutations in the GLB1 gene, which affects the beta-galactosidase enzyme. When these enzymes are deficient, GAGs build up within cells, leading to cellular damage and the syndrome’s varied symptoms.
Inheritance Patterns and Family Risk
Understanding the autosomal recessive inheritance pattern is central to assessing family risk. Individuals who carry one altered gene copy and one normal copy are known as carriers. Carriers typically do not display symptoms because their single functional gene copy is sufficient for normal enzyme activity. Risk arises for offspring when both parents are carriers of the mutated gene.
When two carrier parents have a child, specific probabilities apply to the child’s genetic inheritance. Each child has a 25% chance of inheriting two mutated gene copies and developing Morquio syndrome. There is a 50% chance the child will inherit one mutated and one normal copy, becoming a carrier like their parents. Finally, there is a 25% chance the child will inherit two normal gene copies, meaning they will neither have the syndrome nor be a carrier.
Understanding Population Risk
Morquio syndrome is a rare global disorder. In the United States, its incidence is estimated at 1 in 200,000 to 1 in 300,000 live births. The prevalence of Morquio A can vary significantly worldwide. For instance, birth prevalence estimates for Morquio A have ranged from 1 in 71,000 in the United Arab Emirates to 1 in 500,000 in Japan.
While the syndrome affects males and females equally, certain populations may have a higher prevalence due to genetic factors or historical marriage patterns. Consanguinity (marriage between close relatives) increases the likelihood of both parents being carriers of the same rare gene mutation. This elevates the chance of their children inheriting two altered gene copies, increasing the risk of autosomal recessive conditions like Morquio syndrome within those communities.
Genetic Testing and Risk Assessment
Genetic testing plays a significant role in identifying and managing Morquio syndrome risk. Carrier screening is available for prospective parents, especially if there is a family history of the condition. These tests determine if an individual carries one copy of the mutated GALNS or GLB1 gene, even without symptoms.
Diagnostic testing is performed for individuals suspected of having Morquio syndrome, often initiated by clinical symptoms. This may involve urine tests for elevated GAG levels, enzyme activity assays in blood or white blood cells, and definitive genetic testing using DNA samples. Prenatal diagnosis is an option for at-risk pregnancies, using amniotic fluid cell analysis or chorionic villi sampling. Genetic counseling is a resource for families, providing guidance on interpreting test results and understanding the implications of Morquio syndrome risk.