SNP Shot: Genomic Insights

Glycogen storage disease type IV (GSD IV) is a genetic condition where a complex sugar called glycogen abnormally accumulates in cells. This abnormal glycogen disrupts the normal function of organs and tissues, particularly the liver and muscles. GSD IV has several variations, classified into five types, each characterized by distinct levels of severity, associated signs, and symptoms.

The most severe form, the fatal perinatal neuromuscular type, manifests before birth. An excess of amniotic fluid (polyhydramnios) may be present, along with fluid accumulation in the fetus. These fetuses often exhibit fetal akinesia deformation sequence, resulting in reduced fetal movement, potentially leading to stiff joints (arthrogryposis) after birth. Newborns with this type of GSD IV show very weak muscle tone (severe hypotonia) and muscle loss (atrophy). Sadly, these infants rarely survive beyond the newborn period due to weakness of the heart and respiratory muscles.

The congenital muscular type of GSD IV typically emerges in early infancy, although it may not be noticeable before birth. Infants experience severe hypotonia, affecting breathing muscles. Many also develop dilated cardiomyopathy, where the heart muscle becomes enlarged and weakened, reducing its ability to pump blood efficiently. Infants with the congenital muscular type of GSD IV generally survive for only a few months.

The most frequently observed form of GSD IV is the progressive hepatic type. During the initial months of life, affected infants struggle with weight gain and normal growth (failure to thrive) and develop an enlarged liver (hepatomegaly). These children develop cirrhosis, a form of irreversible liver disease. Portal hypertension (high blood pressure in the vein supplying blood to the liver) and ascites (fluid buildup in the abdomen) may also occur. Around age 1 or 2, hypotonia develops. Children with the progressive hepatic type of GSD IV often succumb to liver failure in early childhood.

The non-progressive hepatic type of GSD IV shares many features with the progressive hepatic type, but the liver disease is less severe. Hepatomegaly and liver disease are typically apparent in early childhood, but cirrhosis usually does not develop. Individuals with this type may also experience hypotonia and muscle weakness (myopathy). While life expectancy varies depending on the severity of symptoms, most individuals with this type survive into adulthood.

The childhood neuromuscular type of GSD IV appears later in childhood and is marked by myopathy and dilated cardiomyopathy. The severity varies greatly; some individuals have only mild muscle weakness, while others experience severe cardiomyopathy and die in early adulthood.

Inheritance:

GSD IV follows an autosomal recessive inheritance pattern. This means that both copies of the gene in each cell must have mutations for the condition to develop. Individuals with an autosomal recessive condition inherit one copy of the mutated gene from each parent, who are carriers but typically do not exhibit signs or symptoms of the condition.