Glycogen Storage Diseases Flashcards
1
Q
What are inborn errors of metabolism and general treatment approaches
A
- IEM: deficiency in an enzyme in a pathway, leading to substrate accumulation and toxic metabolites, leading to symptoms
- approaches: dietary restriction i.e Phe in PKU, toxin removal, substrate removal, replacement (cofactor/enzyme) i.e thiamine in maple syrup urine disease, organ/cell transplantation, product supplementation
2
Q
Groups of glycogen storage diseases
A
- type Ia and Ib: glucose 6 phosphatase and glucose 6 phosphate transporter deficiency. Inability of to do gluconeogenesis or glycogenolysis
- type III, VI, IX: intact gluconeogenesis, but inhibition of glycogenolysis
- type 0, IV, XI: defective storage of glycogen
- type V and VII: only affects glycogen storage in muscle and not liver
3
Q
GSD type IA: heritability, deficiency, symptoms, management
A
- autosomal recessive
- mutation in glucose 6 phosphatase, causes accumulation of glucose 6 phosphate in the ER and pyruvate and lactate
- causes: hypoglycemia, hyperuricemia, elevated lactate, hypertriglyceridemia. Long term complications include growth retardation, hepatocellular adenomas/carcinomas, kidney and bone diseases
- children appear normal at birth, but then have enlarged liver, late growth, seizures and neurocognitive deficits
- treatment goals: maintain adequate BG (4 mmol/L), correct metabolic derangements (elevated lactate, uric acid, TG, cholesterol), provide optimal nutrition to support growth
- restrict: galactose, lactose, fructose, sucrose, excessive fat
- supplement: CHO (uncooked cornstarch- heat and acid can partially digest losing efficacy)
- CHO: 60-70% energy (complex CHO, no fruit and limited vegetables, limit 1 serving dairy per day). For children, CHO needs to be consumed every 3-4 hours, older children and adults can go for 8 hours
- PRO: 10-15% energy (lean sources with high biological value)
- FAT: <30% energy. Limit saturated sources, and ensure essential fatty acid intake
- 2/3 of energy should be given throughout the day, 1/3 at night
4
Q
GSD type III: causes, symptoms, diagnosis, treatment
A
- autosomal recessive
- deficiency in glycogen debranching enzyme in liver and muscle (would convert dextrin to G6P)
- IIIa (liver and muscle), IIIb (liver only)
- leads to fasting hypoglycaemia, hepatomegaly, hepatocellular adenoma/carcinoma, cirrhosis, myopathy, cardiomyopathy
- diagnosed: ketotic hypoglycaemia, elevated CK, hyperlipidemia
- treatment: preventing fasting (frequent feeds), cornstarch, high protein, liver transplant (ONLY for those with severe liver dysfunction). Modified Atkin’s diet is recommended (64% fat, 30% protein, 6% CHO) as improves CK and cardiac function (although adherence is low)
5
Q
GSD type V: deficiency, symptoms, treatment
A
- deficiency of glycogen phosphorylase (cant break down glycogen)
- results in low ATP and muscle contractions. In childhood very low exercise tolerance (can lead to rhabdomyolysis and renal failure)
- treatment: oral administration of creatinine and sucrose before planned exercise. Ketogenic diet to improve substrate concentration for the TCA cycle (ketones) and can greatly improve exercise tolerance
