What is GSD and GSD1b?

Glycogen Storage Disease is a family of inherited metabolic diseases occurring in approximately 1/100,000 births

GSD Type 1 is the most common and is broken into Type 1a and Type 1b.

GSD1b accounts for an estimated 20% of GSD Type 1 cases and is considered ultra-rare with an estimated occurrence of 1 / 1,000,000 births.

GSD1b is caused by a mutation of the gene SLC37A4.

SLC37A4 gene is responsible for the functionality of the Glucose 6 Phosphate Transporter (G6PT) enzyme.

G6PT enzyme is responsible for transporting the stored form of glucose (glycogen) in the liver to glucose during periods of fasting. Due to the lack of function in this enzyme people with GSD type 1b are at risk for hypoglycemia which can results in seizures and death.

Without cornstarch and/or continuous feed, GSD1 would be a mostly fatal disease.

Symptoms include:

Unstable metabolic control – The body can’t break down the storage form of sugar (glycogen) into free glucose (sugar) for use when not eating, which can lead to:

Constant risk of hypoglycemia

Enlarged liver and kidneys

Growth and development challenges

Neutropenia – neutrophils die prematurely and leave people with low white blood cell counts and a weakened immune system.

This is unique to type 1b

Chronic infections

Majority of patients have GI trouble

Many also develop IBD and / or Crohn’s

Current Treatment of GSD1b:

The current treatment protocol aims to maintain metabolic control using a combination of a restrictive diet and scheduled doses of uncooked cornstarch throughout the day and night.

Metabolic Control:

Cornstarch – uncooked cornstarch consumed on average every 2-4 hours (although it varies by person).
Missed or late doses can have very severe consequences that include hypoglycemia, hospitalizations, seizures, and death.
Yes, this includes overnight as well.
Cornstarch is a complex carbohydrate that is slow for the body to break down and helps sustain blood sugar levels without major spikes and drops.
Meticulous Diet – A restrictive diet that is low in sugar (under 5g per meal) and low in carbs.
Timing and quantity are very important. It’s a constant balancing act and patients are often adjusting based on a myriad of reasons like illness, growth, puberty, etc.
Blood Sugar Monitoring – Finger pricks (using a glucometer) are still the most accurate way to monitor blood sugar and verify a low or high, however Continuous Glucose Monitors are now being used more commonly for GSD to help monitor blood sugar trends and alert when a low is coming. Sophie wears a Dexcom, but we still check her finger many times a day.
Feeding Tubes – Although Sophie does not, the majority of children w/ GSD have feeding tubes due to the criticality of cornstarch and diet. Sophie drinks her cornstarch orally mixed with water.

Neutropenia:

G-CSF – Daily injection of Granulocyte colony stimulating factor (G-CSF) to boost white blood cells.
G-CSF has many long-term risks due the stress on the bone marrow, and long-term use has been linked to leukemia.
SGLT2 Inhibitor – A recent discovery of an SGLT2 Inhibitor, called empagliflozin (US brand name Jardiance), has shown promise as a potential alternative to G-CSF or in conjunction with it. We continue to fund research and guideline creation in this area.
Sophie is currently having success with Jardiance, and we have been able to stop the daily G-CSF injections.

Additional Medications / Supplements:

Some patients take over 20 different medications and supplements to help treat symptoms brought on or related to GSD1b.
Many patients take a specific IBD medication.