Carbohydrate Disorders Flashcards
Hereditary Fructose Intolerance
Gene: ALDOB
Aldolase B Deficiency
Apparent in infancy
– when fructose or sucrose added to the diet
– but some formulas contain fructose
* Frequent aversion to sweets
* Signs of symptoms are always observed while
on fructose and resolve off fructose
What are symptoms of acute fructose exposure?
- Symptoms of acute hypoglycemia post-fructose
ingestion (rarely presenting sign) - Vomiting
- Acute liver dysfunction (the most frequent)
- Jaundice
- Bleeding
- Hypoglycemia
- Acidosis
- Renal Fanconi syndrome
- Liver disease/failure
- Seizures, coma, death
Management for fructose exposure
- Elimination of fructose from diet (long lists)
- SUCROSE (table sugar) = glucose + FRUCTOSE
- Danger of IV infusions or oral meds in
emergency room/hospitals - Awareness and information is all that is
required for management - www.bu.edu/aldolase/HFI/treatment/
Fructose-1,6 biphosphatase
deficiency
Gene: FBP2
▪ Triggered by intercurrent illness, fasting, variably
by fructose/sucrose ingestion
▪ Two groups
▪ Newborn
▪ Later-onset
▪ Acute presentation
▪ Hepatomegaly
▪ Hypoglycemia
▪ Lactic acidosis
▪ Ketosis
Management for Fructose-1,6 biphosphatase
deficiency
▪ Avoidance of fasting prevent further episodes
▪ Tolerance to fasting increases with age
Galactose-1-Phosphate
Uridylyltransferase (GALT) Deficiency
Gene: GALT
- Symptoms triggered by lactose/galactose in diet
- Stop milk feeding IMMEDIATELY in an ill infant in
whom you are considering galactosemia
What are the common variants of GALT deficiency?
– p.N314D Duarte (still residual function)
– p.Q188R Classical European ancestry
– p.S135L African ancestry
– 5 kb del Ashkenazi Jewish ancestry
What are signs of GALT deficiency?
Brain damage, pseudotumor cerebri
Cataracts
Jaundice
Enlarged liver and liver failure
Kidney damage (renal Fanconi syndrome)
± Hemolysis
Gram negative sepsis
Premature ovarian insufficiency
Uridine Diphosphate Galactose
4′-Epimerase (GALE) Deficiency
Gene: GALE
- Symptoms
– Severe (rare): similar to GALT deficiency and allo
have psychomotor delays
– Milder variants
Galactokinase (GALK) Deficiency
Gene: GALK
- Cataracts only
- Though recent suggestion of complications
with poor dietary compliance — FTT,
microcephaly, ID, and hypercholesterolemia
Galactose Mutarotase (GALM)
Deficiency
Gene: GALM
- Cataracts only
- Recently described condition, no much
information about long- term outcomes
What is management for the galactosemias?
- Formula: soy or elemental
- Avoid milk and diary products
- Complete restriction of galactose no longer
recommended
What are the clinical presentations for glycogen storage disorders?
- Clinical presentation:
– Liver GSD
– Muscle GSD
– Liver + muscle GSD
– Neurological: Adult form polyglucosan body
disease, GBE1 gene
What are the patterns of inheritance for glycogen storage disorders (GSDs)?
GSD IXa
Gene: PHKA2
* X-linked inheritance
* alpha-2 subunit of hepatic phosphorylase kinase
GSD IXd
Gene: PHKA1
* X-linked inheritance
* alpha-1 subunit of hepatic phosphorylase kinase
How is a GSD diagnosed?
- Molecular testing
- Enzyme level low in blood
- Enzyme deficiency in liver or muscle biopsy (invasive)
GSD Type 0
- GYS2 (liver 0a) and GYS1 (muscle 0b) gene analysis
- Hypoglycemia
- No hepatomegaly
- Treatment: Dietary, regular meals with increased
protein to stimulate gluconeogenesis and complex carbohydrates to provide slow release glucose - Prognosis: Good with dietary control, significant hypoglycemia less frequent in older children and adults
GSD Type 1
- G6PC and SLC37A4 gene analysis
- GSD Ib also has neutropenia (frequent and severe infections)
- Liver adenomas with risk of malignant
transformation
What are clinical features/presentation for GSD Types 0 and 1?
- Hepatomegaly
- Normal liver function
- “Doll face”
- Truncal obesity
- Profound hypoglycemia
- Increased bleeding time
- (↓ Platelet aggregation)
- Growth delay
What is the management for GSD Types 0 and 1?
- Frequent feedings
- Restriction to complex carbohydrates
- Corn starch/glycosade
- Nutrient supplementation
- Allopurinol for hyperuricemia
- Bicarbonate or citrate
- G-CSF for neutropenia in type I non-a
- SGLT2 inhibitors (empagliflozin)
What is GSD Type 0 also called?
Glycogen Synthase
Pompe Disease (GSD II)
Gene: GAA
- Detected on NBS, low acid alpha-glucosidase enzyme level
- Caution pseudodeficiency alleles
- Lysosomal storage disease
- Myopathy»_space; motor delays, FTT, respiratory insuficiency
- Late onset vs infantile (cardiomyopathy and arrhythmias)
- Treatment with enzyme replacement therapy
(Also a lysosomal storage disorder - not covered much in this lecture)
What are clinical features of GSD III?
- Glycogen debranching enzyme (GDE) deficiency
- Hypoglycemia
- Hepatomegaly
- Rhabdomyolysis
- Cardiomyopathy
- Growth and developmental delays
- Treatment: High protein diet, frequent feedings
- Complications: Cirrhosis, liver cancer and distal myopathy
What are clinical features of GSD IV?
Hepatic glycogen phosphorylase deficiency
* Hypoglycemia
* Hepatomegaly
* Rhabdomyolysis
* Growth and developmental delays
* Treatment: Corn starch
* Prognosis: Good, rare liver adenomas, fibrosis and cardiomyopathy
What are clinical features, treatment, and prognosis of GSD V?
- Muscle glycogen phosphorylase deficiency
- Exercise intolerance
- Second wind phenomenon
- Rhabdomyolysis
- Treatment: Ingestion of glucose source prior to exercise and avoidance of strenuous effort during exercise
- Prognosis: Good
