Glycogen storage disease type III, also known as Cori's disease, Forbes disease or limit dextrinosis, is characterized by deficiency of the cytosolic debrancher enzyme.
The clinical manifestations are nonmyopathic even though the enzyme is readily seen in all tissues. The patient history is made of infant seizures. Hepatomegaly and growth retardation are other common features.
Muscle weakness progresses very slowly and vigorous exercise is not associated with tenderness, cramping and myoglobulinuria . Cortical malformations are also reported in many cases. Polymicrogyria is rarely reported but is an important symptom.
GSD type 3a is more common and the prognosis is much more unfavorable than GSD type 3b. The major clinical features of GSD type 3a are Cardiomegaly and cardiomyopathy, muscular weakness and atrophy (especially around the limb musculature), hepatomegaly (with or without splenomegaly) and general cardiac and skeletal muscle abnormalities.
GSD type 3b is less common and it is seen roughly 15% of the time. It is more favorable prognostically than GSD type 3a. With GSD type 3a, the liver is the only organ involved.
Hepatosplenomegaly is moderate while mild fibrosis and micronodular cirrhosis of the liver are rare and clinically silent. Hepatomegaly is pronounced during childhood but usually normalizes when the individual gets to puberty . Patients with GSD type 3b reach their expected height as growth is accelerated at puberty.
Baseline levels of CK do not exclude GSD type 3. In GSD type 3b, serum aminotransferase levels are elevated during childhood but usually normalize at puberty.
Usually, serum lactate and uric acid levels are in the reference range. In GSD type 3, echosonography may be utilized. This noninvasive method that can provide useful information about the size of the liver, spleen, and heart .
There is no specific treatment for GSD Type III. If hypoglycemia occurs, the patient should consume frequent high-protein meals.
The prognosis of GSD type III is much better than what is obtainable with GSD type I Many patients with GSD type III survive to adulthood.
GSD type 3b is a milder form of the disease, while in GSD type 3, the prognosis depends a lot on the cardiac system .
The GSD type 3 is caused by a deficiency in the debrancher enzyme. The deficit of this enzyme is confined to the liver in GSD type 3b but in GSD type 3a, the deficit can be seen in the skeletal muscles and the myocardium.
With this type of GSD, there is a correlation between the severity of clinical presentation and residual enzyme activity . The debrancher enzyme is coded by a gene mapped to band 1p21. In patients spanning different ethnicities, more than 30 different mutations of the gene have been identified.
The disease is normally inherited as an autosomal recessive trait and prenatal diagnosis and carrier detection are possible by DNA mutation analysis.
Internationally, the incidence and frequency of inherited metabolic conditions place the occurrence of GDs type 3 at 2.3 children per 100,000 live births .
The hypoglycemic seizures that occur in the first decade of life may lead to immediate morbidity.
Hepatic disease and progressive muscle weakness are the major causes of long term morbidity.
With an enzyme defect, carbohydrate metabolic pathways get blocked and excess glycogen accumulates in affected tissues. Each GSD represents a specific enzyme defect, and the enzyme is in specific or most of the body tissues.
The enzyme amylo-1,6-glucosidase is deficient and this leads to the accumulation of dextrin. The site of glycogen accumulation is cytoplasmic most of the time. Conversion is usually a one-way reaction from glycogen into glucose-1,6-phosphate . The enzyme is seen in all tissues.
The disease results from a pan-deficiency of the enzyme (GSD 3a) and muscle-specific retention of glycogen debranching enzyme (GSD 3b). The condition is autosomal recessive. No common mutation has been described in Cori disease (types a and b), although 2 alleles have been reported for GSD 3b and 1 allele has been found in North African Jewish people with GSD 3a.
Although the most prevalent mutations have been reported in the North African Jewish population and in an isolate such as the Faroe Islands, 3 novel mutations and 5 known mutations among 22 Tunisian patients with GSD 3 was recorded in the past.
The GSD type 3b arises due to mutation in exon 3 of the glycogen debranching enzyme. Different haplotypes of GSD type 3a have also been recorded. GSD 3 does not only occur in humans. It can equally be found in other mammals .
There are no guidelines for prevention of GSD Type III.
Glycogen storage disease type III is an inherited error of metabolism which is characterized by the deficiency in enzymes that debranch glycogen . The condition is an autosomal recessive metabolic disorder.
The GSD type 3 is equally referred to as the Cori disease in honor of the 1947 Nobel laureates Gerty Cori and Carl Cori. Other names for this condition are the limit dextrinosis and the Forbes disease, honoring the American physician Gilbert Burnett Forbes who expanded the features of this disorder even further.
Glycogen is the body’s molecule for storing carbohydrate energy. The symptoms consistent with GSD type 3 are caused when there is a deficiency of the debrancher enzyme or the amylo-1,6 glucosidase. When this is the case, abnormal glycogen gets deposited in the liver, muscles and in some rare cases, heart. The GSD type 3 has two sub types A and B.
Parents need to be fully educated about the genetic implications of this disorder. It is hereditary and thus it runs in families.
Therefore, if anyone you know in your family or one of your children or even you have this defect, the doctor will direct you to a specialist in genes (geneticist). With your full co-operation, this expert will be able to tell you what the chances are for your next child to be diagnosed with this condition.
If as a mother you are already pregnant, it is still possible to have some tests carried out very early into the pregnancy. This will help you to figure out if the unborn child has the GSD Type III or not.
The test is pretty straightforward and involves taking a sample of the amniotic fluid (fluid from around the baby in your womb). With this, the doctor will be able to study the makeup of the enzyme and fully determine if the unborn child has glycogen disorder or not.
If you have a child that has been diagnosed with the disease, you don’t need to panic as the outlook for this condition is positive. Most people with the condition respond well to treatment as long as they are judiciously adhered to. Your doctor will discuss in detail all you need to know regarding treatment.