Glycogen Storage Disease Type Ia

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There are two types of glycogen storage disease type I. Glycogen storage disease type Ia is caused by mutations (changes) in the G6PC gene and glycogen storage diseases type Ib is caused by mutations in the SLC37A4 gene.  

The proteins made by the G6PC and SLC37A4 genes work together to break down glucose 6-phosphate (a type of sugar molecule). This breakdown produces glucose (a simple sugar) which is the main source of energy for most cells in the body.  

Mutations (changes) in the G6PC and SLC37A4 genes disrupt the breakdown of glucose 6-phosphate. The glucose 6-phospate that cannot be broken down to glucose is converted (transformed) into glycogen and fat and stored within the cells. Too much glycogen and fat built up within the cells can be toxic and will damage organs and tissues including the liver and kidneys. This damage causes the symptoms of GSD type Ia.  

The overall prevalence of GSDI is 1 in 100,000 individuals. The prevalence of GSDI in Ashkenazi Jews is estimated to be 1 in 20,000. GSDI affects males and females in equal numbers in all populations.  

GSD type Ia is more common than GSD type Ib. GSD type Ia accounts for 80% of all GSD type I cases.  

Symptoms will vary from patient to patient and not all individuals with the conditions will have all the symptoms listed below.  

Some new-borns with GSD type Ia present with severe hypoglycaemia (low blood sugar), however, it is more common for infants around the age of three to four months to present with hepatomegaly (enlarged liver), lactic acidosis (build-up of lactate in the body), hyperuricemia (high blood uric acid levels), hyperlipidaemia (raised lipids in the blood), and hypoglycaemic (low blood sugar) seizures. 

80-99% of patients have these symptoms:  

• cognitive impairment (abnormal cognition) 
• full cheeks (apple cheeks)  
• hyperlipidaemia (raised lipids in blood) 
• hyperuricemia (high blood uric acid levels) 
• hypoglycaemia (low blood sugar) 
• muscular hypotonia (low or weak muscle tone) 
• recurrent respiratory infections (frequent respiratory infections) 
• seizures  
• short stature (decreased body height)  

5-29% of patients have these symptoms:  

• Xanthomatosis (yellow bumps of fatty deposits on skin)  

Other possible symptoms:  

• Abnormal bleeding  
• Decreased muscle mass 
• Delayed puberty  
• “Doll-like” facial appearance  
• Elevated hepatic transaminase (high liver enzymes)  
• Enlarged kidney  
• Gout (a form of arthritis) 
• Focal segmental glomerulosclerosis (scarring in the kidney)  
• Hepatocellular carcinoma (liver cancer) 
• Hepatomegaly (enlarged liver)  
• Hypertension (high blood pressure)  
• Intermittent (irregular) diarrhoea  
• Lactic acidosis (increased lactate in the body)  
• Lipemia retinalis (abnormal appearance of arteries and veins in the eyes) 
• Nephrolithiasis (kidney stones)  
• Osteoporosis (disease reducing bone quality and density)  
• Pancreatitis (inflammation of the pancreas)  
• Proteinuria (urine containing an abnormal amount of protein) 
• Protuberant abdomen (belly sticking out) 
• Xanthelasma (yellowish plaques occurring on the inner part of the eyelids)  

The condition is diagnosed through specialised blood and urine tests that will show abnormal levels of glucose, lactate, uric acid, triglycerides and cholesterol.  

A liver biopsy may also be used to show specific enzyme deficiencies.   

The diagnosis can be confirmed through molecular genetic testing which will show mutations (changes) in the G6PC gene. Molecular genetic testing can also be used for prenatal (before birth/during pregnancy) diagnosis or carrier testing.  

This condition can be treated using a special diet to normalise glucose levels, prevent hypoglycaemia (low blood sugars) and help with growth and development of the individual. The diet includes frequent small servings of carbohydrates during the day and night and should be maintained throughout life. Please be noted that any dietary changes require specialist dietitian’s advice and monitoring. 

Supplements including calcium, vitamin D and iron supplements may be recommended in order to prevent deficits. Frequent feedings of uncooked corn starch may also be used in order to maintain and improve blood glucose levels.  

Different medications can be used to treat symptoms associated with GSD type Ia including gout, low lipid levels and preventing or treating kidney disease.  

Kidney and liver transplantations are sometimes necessary if no other treatments are successful.  

Patients with this condition should be monitored at least once a year with kidney and liver ultrasounds and routine blood tests.  

Glycogen storage disease type 1a is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.  

The pattern of inheritance of GSD type 1a is autosomal recessive. This means that carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with GSD type 1a deficiency are carriers.   

When both parents are carriers, the risk to the baby in each pregnancy is  

• 25% chance (1 in 4) of developing the condition  
•  50% chance (1 in 2) for the baby to be a carrier of the condition  
•  25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier  

Genetic counselling can be requested to get a full explanation.  

For more information, please visit Association for Glycogen Storage Disease UK.

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002].