Von Gierke’s Disease

Von Gierke’s Disease

It is also called Glycogen Storage Disease type 1. It is an autosomal recessive disorder that results in improper metabolism of glycogen in the body.

It is divided into two types:

Type Ia: It is caused by deficiency of Glucose-6-Phosphatase enzyme.

Type Ib: It is caused by deficiency of Glucose-6-Phosphate Translocase.

It occurs in 1 in 100,000 live births.

Biochemical Abnormalities

1.    Because of absence of Glucose-6-Phosphatase enzyme, Liver is not able to liberate free glucose from glycogen. This results in an inability to regulate blood sugar and leads to fasting hypoglycemia.

2.    Increased Glucose-6-Phosphate leads to increased Glycolysis, which in turn leads to increased production of Lactic Acid and manifests Lactic Acidosis.

3.    Because blood glucose is low, Insulin production is also decreased. This results in reduced uptake of triglycerides and causes hypertriglyceridemnia.

4.    Excess Glucose-6-Phosphate leads to increased functioning of Pentose Phosphate pathway. This results in increased nucleotide production which then leads to Hyperuricemia, due to metabolism of nucleotides.

5.    Exhaustion of oxaloacetate by increased functioning of TCA cycle leads to channeling of excess Acetyl-CoA produced into ketone body synthesis, which causes Ketosis.

Clinical Manifestations

1.    Fasting Hypoglycemia. This is not responsive to administration of adrenaline due to block at a level above the action of adrenaline.

2.    Hyperlipidemia, Lactic Acidosis and Ketosis due to defective glucose homeostasis.

3.    Hyperuricemia due to increased functioning of pentose phosphate pathway.

4.    Hepatomegaly and Splenomegaly are seen. Liver enlargement can also progress to Liver Cirrhosis.

5.    Non-Alcoholic Fatty Liver is seen due to deposition of triglycerides in Liver.

6.    Osteopenia (low bone density) is observed.

7.    Kidney failure occurs due to prolonged lactic acidosis, which can present as Fanconi Syndrome.

8.    In some cases, Impaired platelet aggregation is observed.

Treatment

The priority is to compensate for the inability of Liver to produce blood glucose by near constant administration of glucose or cornstarch (easily digested to give glucose and inexpensive). This is to be done in such a manner that the child doesn’t go for more than 3 to 4 hours without intake of glucose.

This is done to ensure the long-term complications of hypoglycemia do not arise. The diet should contain 65-70% of carbohydrates.

Type Ib:

In this, the same symptoms as Type Ia appear, except for neutropenia observed in these patients.

Neutropenia occurs due to defective intake of glucose by neutrophils, which in turn is due to a defect in the glucose-6-phosphate transporter.