Glycogen Storage Diseases and Inborn Errors of Galactose and Fructose Metabolism Flashcards
(33 cards)
GSD I symptoms
*deficiency in glucose-6-phosphatase
- hepatomegaly, but normal liver function –> protruding abdomen
- “doll face”
- truncal obesity
- profound hypoglycemia after meal (contrary to FAO disorders)
- hyperlactacidemia
- hyperuricemia
- hyperlipidemia, primarily hypertriglyceridemia (suggests increased cardiovascular risk)
- increased bleeding time, perhaps due to decreased platelet aggregation
- growth retardation
GSD 1b symptoms
1/5 of patients with GSD1; have all symptoms of GSD 1 plus:
- neutropenia (low white blood cell count); neutrophil dysfuntion (impaired motility and migration)
- risk of frequent and severe infections that can affect upper and lower respiratory tract, the skin, the urinary tract
- protracted diarrhea, inflammatory bowel disease
GSD I Complications
- short stature
- gout
- osteoporosis
- nephropathy
- pulmonary hypertension
- liver adenomas with risk of malignant transformation
- polycystic ovaries
- necrotizing pancreatitis
Diagnosis of GSD I
- fasting profile
- enzyme assay
- molecular (genetics)
Characteristic fasting profile
Measure G6Pase activity + glycogen concentration in liver tissue
Enzyme assay
- measure released free phosphate
- measure protein concentration of liver homogenate
Molecular
- normal cell count–> G6PC = GSD 1A.
- neutropenia –> G6PT1 = GSD 1b
- if both genes show no mutation, back to start of specific assays in liver
GSD I conventional treatment
MAIN GOAL: do not let patient become hypoglycemic
- frequent feedings (avoid fasting mode)
- restruct complex carbs
- cornstarch supplement
- night-time nasogastric tube feedings
- nutrient supplementation
- ALLOPURINOL for hyperuricemia
- bicarbonate or citrate
- G-CSF for neutropenia
- ACE inhibitor
GSD I and liver transplantation
GSD Ia patients may have liver adenoma
- corrects metabolic abnormalities
- neutropenia persists in GSD I non-a
- reserved for patients with liver adenoma (+malignant growth)…but no good early markers
- not standard of care because there are effective dietary therapies
Short fasting in GSD I
glucose is decreasing more rapidly than in controls, lactate increases. In controls, lactate does not increase
Excess lactate –> metabolic acidosis
GSD III (Cori, Forbes) etiology
deficiency of glycogen debranching enzyme
GSD IIIa –> liver and muscle
GSD IIIb –> only liver
as opposed to GSD I, no fasting lactic acidemia, but they do have slight postprandial hyperlactatemia
GSD III (Cori, Forbes)
- symptoms
- findings
SYMPTOMS
- hepatomegaly
- protruding abdomen
- normal kidneys
- growth delay
- muscle weakness
FINDINGS
- hypoglycemia
- hyperlipidemia
- elevated creatine kinase (CK)
- peripheral neuropathy
- cardiomyopathy
Minimal fasting in GSD III
rapid, progressive hypoglycemia
rapid elevation of ketone bodies
no acidosis –> lactate plus ketones is low enough
Diagnosis of GSD III
suspected in infancy
- metabolic profile: look for ketotic hypoglycemia, normal lactate at short fast
- elevated CK
measure debranching enzyme in leukocytes, RBCs, fibroblasts
DNA investigation
- IIIb - exon 3
- IIIa - beyond exon 3
GSD III
- treatment
- complications
TREATMENT
- high protein diet (carbs will accumulate)
- frequent feedings if hypoglycemia
- supplement 3-OH butyrate
COMPLICATIONS
- liver cirrhosis
- liver cancer
- muscle hypotonia and wasting developing with age
GSD VI (Hers)
- deficient in what enzyme?
- genetics
Liver phosphorylase deficiency
Gene defect PYGL on chromosome 14, autosomal recessive
GSD VI (Hers) symptoms
isolated hepatomegaly
growth/motor development delay
mild fasting hypoglycemia and fasting ketosis
hyperlipidemia and elevated LFTs
GSD VI (Hers)
- diagnosis
- treatment
- prognosis
DIAGNOSIS
- enzyme assay: liver biopsy
- molecular diagnosis (PYGL) most common
TREATMENT
- avoid prolonged fasting and alcohol
PROGNOSIS: most symptoms resolve at puberty
GSD IXa etiology
X-linked; affects only males
liver phosphorylase B-kinase deficiency
PHKA2 on chr X
similar to, more common than GSD VI
GSD IXa symptoms
isolated hepatomegaly
growth/motor development delay
mild fasting hypoglycemia + ketosis
hyperlipidemia and elevated LFTs
muscle involvement
GSD IXa
- diagnosis
- treatment
- prognosis
DIAGNOSIS
- enzyme assay in RBC, might need tissue for isoenzymes
TREATMENT
- dietary; bedtime snack
PROGNOSIS
- Benign, most symptoms resolve during puberty (ie hepatomegaly and failure to grow resolves)
GSD 0
- deficiency of what?
- genetics
deficiency of either:
- liver glycogen synthase (GYS2)
- muscle glycogen synthase (GYS1) (expressed in muscle AND liver)
GYS1 and 2: 70% homologous, located on diff chromosomes
frequently not diagnosed because it mimics functional ketotic hypoglycemia
GSD 0 symptoms
fasting-induced ketotic hypoglycemia with normal lactate
drowsiness, fatigue
convulsions
no hepatomegaly
often: postprandial hyperglycemia and hyperlactacidemia with glycosuria
GSD 0
- diagnosis
- treatment
- prognosis
DIAGNOSIS
- molecular genetic analysis of GYS2
- Enzyme assay requires liver biopsy
TREATMENT
- dietary
PROGNOSIS: good, but females at risk of hypoglycemia during pregnancy
GSD V (McArdle)
- deficiency in what?
- genetics
myophosphorylase deficiency
PYGM gene on chromosome 12q13
GSD V (McArdle) symptoms
child-onset exercise intolerance
brief exertion may cause muscle cramps, myoglobinuria, hyperuricemia, mild CPK elevation
GSD V (McArdle)
- diagnosis
- treatment
- prognosis
DIAGNOSIS
- bicycle/treadmill test to detect increased uric acid and ammonia
- if treadmill test is abnormal, enzyme assay
TREATMENT
- avoid strenuous exercise
- protein-rich diet, glucose, fructose
good prognosis
