The major sign of GSD type 1 is the enlargement of the kidney and livers. In the first few weeks of life, the liver remains in its normal size. It gradually enlarges thereafter leading to symphysis in many patients. Enlargement of the abdomen due to hepatomegaly is one of the first signs noted by the mother of the patient .
The face of the patient is often round, and this is due to the deposition of fat. Mental develop often proceeds normally but growth is retarded. Unless otherwise expected from the genetically determined potential of their families, children with GSD type 1 condition never gain height commensurate with their age. The height is often below the third percentile for their age. The onset of puberty is often delayed.
In patients who are older than 20 years of age, hypertension, tubular defects, renal stones and renal function disturbance are some of the late complications of this disease condition. In many cases, dialysis and transplantation will be required as the deterioration of renal function will gradually progress to terminal insufficiency .
In individuals suffering from GSD type 1, serum glucose and blood pH levels are often decreased but the cholesterol levels, triglyceride, serum lactate and uric acid are elevated . The creatinine levels and urea may be elevated when renal function is impaired.
Other important laboratory values that must be obtained include: CBC and differential (eg, anemia, leukopenia, neutropenia), Gamma glutamyltransferase level, Serum triglyceride and cholesterol levels, Serum uric acid level, Blood pH, Serum lactate level, serum glucose, electrolyte levels, Serum alkaline phosphatase, calcium, phosphorus, urea, and creatinine levels,Urinary excretion levels of uric acid and calcium, Urinalysis for aminoaciduria, proteinuria, and microalbuminuria in older patients and Coagulation.
One important imaging test that must be carried out is liver and kidney ultrasonography. This needs to be performed for follow up of organomegaly and detection of hepatic adenomas and nephrocalcinosis.
There is only symptomatic treatment available, which is very important. The main goal is to avoid hypoglycemia and maintain a normoglycemic state.
As long as the available dietary and medical measures are implemented, the prognosis is much better than what it used to be in the past .
GSD type 1a: This subtype of GSD type 1 is caused by deficiency of hydrolase or G6pase. G6pase is an integral membrane protein and so, mutations in the protein’s transmembrane helices lead to the most severe enzyme activity deficiency.
GSD type 1b: This subtype of GSD is caused by deficiency of G6PT1. The G6PT1 gene is expressed in the hematopoietic progenitor cells, liver and kidney, it contains 8 exons and covers approximately 5kb.The gene had been mapped to band 11q23 .
The mutated allele is an inheritable autosomal recessive trait. The type of mutation in the G6PT gene and the severity of the disease don’t have any correlation. Therefore, other factors are believed to be responsible for the expression of different symptoms recorded. Neutropenia in patients for instance greatly influences the severity and the general course of the disease.
Patients with GSD type 1 account for 24.6% of all patients suffering from glycogen storage disease. In GSD type 1, acute hypoglycemia may be fatal. Early death is no longer common due to the improvements in care and treatment.
Mortality is caused on adolescent and adults patients by hypertension, malignant alteration of hepatic adenomas, hypertension and renal failure. No racial or ethnic differences exist for GSD type 1 . As it is with most genetic conditions, GSD type 1 develops at conception but the first signs of the disease appear at birth or much later.
When there is insufficient G6Pase activity, G6p cannot be converted into free glucose. However, G6P is metabolized into lactic acid which ends up being incorporated into glycogen. In this manner, large amounts of glycogen are formed and stored away as molecules that have normal structure in the hepatocytes cytoplasm and the cells of the renal and intestinal mucosa . This leads to the enlargement of the kidneys and liver which is the major clinical presentation of this disease. The major biochemical alteration recorded is hypoglycemia and hyperucemia, hyperlipidemia, metabolic acidosis and hyperlactatemia are common secondary abnormalities.
With hypoglycemia, the G6pase deficiency stops the glycogen degradation process and gluconeogenesis within the liver. This prevents the production of free glucose molecules. It is a result of this, that patients who have GSD type 1 present fasting hypoglycemia. Endogenous glucose formation is not fully inhibited though irrespective of the metabolic block. In young patients however, the free glucose produced only reaches 50% of the production recorded by healthy individuals. Adults on the other hand produce as much as two thirds of the healthy amount of free glucose. Hypoglycemia inhibits secretion of insulin and this stimulates the release of cortisol and glucagon .
There are no guidelines for prevention of Glycogen storage disease type I.
Glycogen storage disease type I commonly known as GSD I or von Gierke’s disease is the most common amongst the different glycogen storage conditions. The condition is genetic and it arises in the presence of a glucose-6-phosphate deficiency .
The deficiency of this enzyme leads to impairment in the liver’s ability to produce free glucose from glycogen and through gluconeogenesis. Severe hypoglycemia is caused because the aforementioned processes are the only way through which a body in fasting receives glucose from the body. With severe hypoglycemia, the liver and kidneys see increased glycogen storage. This may lead to the enlargement of both organs. In childhood, the organs may function normally but towards adult hood, the organs are susceptible to a variety of problems .
Hyperlipidemia and lactic acidosis are some other metabolic derangements that arise due to this condition. The condition was named after Edgar von Gierke. He was the German doctor that discovered the condition. The condition is made of two subtypes GSD type 1a and GSD type 1b.
Parents and adult patients need to understand the measures required to control hypoglycemia and all other indeed all such related ailments. These measures will generally include proper care and nutrition.
Parents also need to understand the importance of continuous overnight feeding through a nasogastric tube. They need to learn how to correctly place the tube on their own to control the entire feeding process.
The treatment the individuals will be subjected to will vary due to various factors but the focus for most of the treatments is to help the patient stabilize the energy levels and blood sugar throughout the body. To achieve this, cornstarch or nutritional supplements like glucose is used. In some cases, the health professionals will recommend a high protein diet as these often prove helpful in the treatment of this condition.
For those who do not respond to treatments after taking the nutritional supplements for a while, there may be need for liver transplant. Also as protection against infection, antibiotics will be recommended by your health expert. Sticking judiciously to the prescription is very important.
Finally depending on the severity of the symptoms, the patient may have to undergo clinical treatment that is focused on the replacement of enzymes that are not working as should. In many cases, this treatment will reverse heart problems, muscle weaknesses etc.