We present the case of a 23-year-old female who was diagnosed with GSD type Ia shortly after birth.
Q What is the other name of GSD type 1a ?
It is also known as Von Gierke’s disease.
Q What is the defect in Von Gierke’s disease?
It is a glycogen storage disorder with absence of Glucose – 6 phosphatase enzyme.
Q What are the clinical features of this disease ?
Glucose 6 phosphatase enzyme is required by both the Gluconeogenesis pathway and glycogenolysis pathway for production of glucose. Since the patient has absent glucose-6-phosphatase enzyme the patient generally develops fasting hypoglycemia which can be severe along with metabolic acidosis during infancy. Apart from this there is accumulation of glycogen in liver, leading to hepatomegaly and renal enlargement. There is also shunting to the uric acid pathway leading to hyperuricemia. There is also elevated triglycerides.
Q What are the difference in GSD Ia and Ib ?
Type 1b is mainly because of defect in translocase enzyme that transfer the glucose-6-phosphtase across the microsomal membrane. Apart the clinical symptoms described above these people also have neutropenia and increase risk of bacterial infections.
She was hospitalized for the first time at the age of 6 months for hypoglycaemia and metabolic acidosis that occurred during a respiratory infection. She had a doll-like facial appearance, hepatomegaly and kidney enlargement. She had been repeatedly hospitalized for episodes of enormous hypoglycaemia during infancy and adolescence.
Q What is the management of hypoglycemia is patient with GSD 1a ?
Hypoglycemia is generally managed by frequent feeding especially using uncooked corn-starch.
Q What is the role of uncooked corn-starch in endocrinology ?
It is a complex carb that is slowly broken down over 2-6 hrs. If taken at night time- it can prevent nocturnal hypoglycemia. EXTEND BAR is a popular preparation of uncooked corn-starch.
The patient was treated out of hospital with frequent meals rich in carbohydrates during the day and every 2–3 h during the night and as a result she developed obesity. Besides nutritional therapy, she was also treated with allopurinol for hyperuricaemia.
Q What are the long term complications of Von Gierke’s disease ?
- Short stature
- Delayed puberty
- PCOS like morphology in ovaries (without hirsutism and hyperandrogenism)
- Risk of hepatic adenoma and hepatocellular carcrinoma
- Risk of proteinuria and renal failure.
- Risk of pancreatitis
She came to our clinic at the age of 22 years for the diagnostic evaluation of arterial hypertension and dyslipidaemia. Her weight was initially 80 kg, height was 157 cm and BMI was 32.5. The levels of uric acid were 425 nmol/l, LDL 3 mmol/l, HDL 0.8 mmol/l, cholesterol 5.2 mmol/l and TG 2 mmol/l. Her in-office blood pressure measurement repeatedly showed raised values (160/90 mmHg in average). We carried out a 24-h ambulatory blood pressure monitoring, which revealed normal daily and average 24-h values of both systolic and diastolic pressure, but also the non-dipping pattern of systolic pressure during the night. The latter can be attributed to excessive nocturnal eating and consequently disturbed sleeping pattern.
The patient used to control glycaemia with self-measurements, mostly in preprandial periods, and results were recorded in a blood glucose diary. The self-measurements were made only during the daytime and revealed no abnormal excursions of glucose levels in either direction.
It has been shown previously that glucose levels obtained by continuous subcutaneous glucose monitoring (CGM) correspond to those obtained by venous blood sampling or self-measurements. To evaluate the actual prevalence of eventual hypoglycaemic episodes, we proposed CGM during a 72-h period.
Glucose levels <3 mmol/l with symptoms that are relieved promptly when glucose levels are raised document hypoglycaemia. The results of CGM revealed no episodes of hypoglycaemia (the sensor was calibrated to the glucose range between 3.5 and 8.5 mmol/l). Instead, several episodes of postprandial hyperglycaemia were recorded (Fig. 2a, b and c).
The patient was advised by the nutritionist to change her dietary regimens. She reduced the quality and quantity of meals and cut out the candy syrup that she was using frequently for many years because of the fear of hypoglycaemia. She was advised to use cornstarch instead.
She used 400 g of cornstarch initially and only 250 g/day later on.
Q Apart from the corn-starch which is other way of preventing nocturnal hypoglycemia in such children ?
We can insert a nasogastric tube and start a continuous nocturnal gastric drip to prevent nocturnal hypoglycemia.
The patient came to our clinic at the age of 22 years for the diagnostic evaluation of arterial hypertension and dyslipidaemia. Her BMI was 32.5 at the time. The results of 72-h CGM revealed fluctuations in her blood glucose levels and allowed us to advise her to change her dietary regimens. She reduced the number and quantity of meals and lost 11 kg with a consequent decrease in BMI from 32.5 to 28 within a year.
Her lipid status also improved with an increase in the levels of HDL (1.2 mmol/l) and a decrease in the levels of TG (1.8 mmol/l), cholesterol (5 mmol/l), LDL (2.8 mmol/l) and uric acid (366 nmol/l).
Learning points from this case
- Fasting hypoglycemia is a clinical feature of Von Gierke’s disease
- Uncooked corn-starch can be used to prevent nocturnal hypoglycemia
- Patient with Von Gierke’s disease can develop serious problems in adulthood which include obesity, PCOS, gout, osteoporosis, dyslipidemia, hepatic adenomas, renal failure etc.