Glycogen Storage Diseases (GSDs)

Description

Glycogen storage diseases (GSDs) are a group of genetic disorders that affect the way your body stores and breaks down glycogen, a type of sugar that provides energy. This can lead to a variety of symptoms, depending on the specific type of GSD. While there is no cure for GSDs, there are treatments that can help manage the symptoms and improve quality of life.

Genes Involved

Genes Involved in GSDs:

G6PC: Glucose-6-phosphatase (G6PC) deficiency (GSD type Ia)
SLC37A4: Glucose-6-phosphate transporter deficiency (GSD type Ib)
PFKLB1: Phosphofructokinase, liver (PFKL) deficiency (GSD type VII)
AGL: Acid alpha-glucosidase deficiency (Pompe disease)
GAA: Alpha-glucosidase deficiency (GSD type III)
GBE1: Glycogen branching enzyme deficiency (GSD type IV)
PYGM: Muscle glycogen phosphorylase deficiency (McArdle‘s disease)
PHKA1: Phosphorylase kinase, liver (PHKA1) deficiency (GSD type IX)
PHKA2: Phosphorylase kinase, muscle (PHKA2) deficiency (GSD type IX)
PHKB: Phosphorylase kinase, brain (PHKB) deficiency (GSD type IX)
PHKG2: Phosphorylase kinase, gamma subunit deficiency (GSD type IX)
GYS1: Glycogen synthase deficiency (GSD type 0)
GYS2: Glycogen synthase 2 deficiency (GSD type 0)
LKB1: Liver kinase B1 (LKB1) deficiency (GSD type X)
ENO3: Enolase 3 deficiency (GSD type XIII)

Recognizing the Signs and Symptoms

Recognizing the signs and symptoms of GSDs is crucial for early diagnosis and management. Common symptoms include:

Hypoglycemia: Low blood sugar levels, leading to fatigue, weakness, sweating, and in severe cases, seizures.
Hepatomegaly: Enlarged liver due to glycogen accumulation.
Muscle weakness and cramps: Difficulty with physical activity.
Delayed growth and development: In some cases, GSDs can affect growth and development.
Other symptoms: Depending on the type of GSD, other symptoms may include kidney problems, heart problems, and respiratory issues.

Causes

GSDs are caused by mutations in genes that are responsible for the production of enzymes involved in glycogen metabolism. These mutations can prevent the body from properly storing or breaking down glycogen, leading to a buildup of glycogen in the liver, muscles, or other tissues.

Inheritance/recurrence risk

Most GSDs are inherited in an autosomal recessive pattern. This means that both parents must carry a copy of the mutated gene for their child to inherit the disease. If both parents are carriers, there is a 25% chance their child will inherit the disease, a 50% chance their child will be a carrier, and a 25% chance their child will not inherit the disease. However, some types of GSDs can be inherited in an autosomal dominant pattern, which means that only one copy of the mutated gene is needed to inherit the disease.

WES Whole Exome Sequencing