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MedGen 2 > Glycogen Storage Diseases and Inborn Errors of Galactose and Fructose Metabolism > Flashcards

Glycogen Storage Diseases and Inborn Errors of Galactose and Fructose Metabolism Flashcards

1
Q

GSD I symptoms

A

*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
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2
Q

GSD 1b symptoms

A

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
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3
Q

GSD I Complications

A
  • short stature
  • gout
  • osteoporosis
  • nephropathy
  • pulmonary hypertension
  • liver adenomas with risk of malignant transformation
  • polycystic ovaries
  • necrotizing pancreatitis
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4
Q

Diagnosis of GSD I

  • fasting profile
  • enzyme assay
  • molecular (genetics)
A

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
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5
Q

GSD I conventional treatment

A

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
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6
Q

GSD I and liver transplantation

A

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
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7
Q

Short fasting in GSD I

A

glucose is decreasing more rapidly than in controls, lactate increases. In controls, lactate does not increase
Excess lactate –> metabolic acidosis

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8
Q

GSD III (Cori, Forbes) etiology

A

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

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9
Q

GSD III (Cori, Forbes)

  • symptoms
  • findings
A

SYMPTOMS

  • hepatomegaly
  • protruding abdomen
  • normal kidneys
  • growth delay
  • muscle weakness

FINDINGS

  • hypoglycemia
  • hyperlipidemia
  • elevated creatine kinase (CK)
  • peripheral neuropathy
  • cardiomyopathy
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10
Q

Minimal fasting in GSD III

A

rapid, progressive hypoglycemia
rapid elevation of ketone bodies
no acidosis –> lactate plus ketones is low enough

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11
Q

Diagnosis of GSD III

A

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
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12
Q

GSD III

  • treatment
  • complications
A

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
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13
Q

GSD VI (Hers)

  • deficient in what enzyme?
  • genetics
A

Liver phosphorylase deficiency

Gene defect PYGL on chromosome 14, autosomal recessive

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14
Q

GSD VI (Hers) symptoms

A

isolated hepatomegaly
growth/motor development delay
mild fasting hypoglycemia and fasting ketosis
hyperlipidemia and elevated LFTs

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15
Q

GSD VI (Hers)

  • diagnosis
  • treatment
  • prognosis
A

DIAGNOSIS

  • enzyme assay: liver biopsy
  • molecular diagnosis (PYGL) most common

TREATMENT
- avoid prolonged fasting and alcohol

PROGNOSIS: most symptoms resolve at puberty

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16
Q

GSD IXa etiology

A

X-linked; affects only males
liver phosphorylase B-kinase deficiency

PHKA2 on chr X

similar to, more common than GSD VI

17
Q

GSD IXa symptoms

A

isolated hepatomegaly
growth/motor development delay
mild fasting hypoglycemia + ketosis
hyperlipidemia and elevated LFTs

muscle involvement

18
Q

GSD IXa

  • diagnosis
  • treatment
  • prognosis
A

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)

19
Q

GSD 0

  • deficiency of what?
  • genetics
A

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

20
Q

GSD 0 symptoms

A

fasting-induced ketotic hypoglycemia with normal lactate
drowsiness, fatigue
convulsions
no hepatomegaly
often: postprandial hyperglycemia and hyperlactacidemia with glycosuria

21
Q

GSD 0

  • diagnosis
  • treatment
  • prognosis
A

DIAGNOSIS

  • molecular genetic analysis of GYS2
  • Enzyme assay requires liver biopsy

TREATMENT
- dietary

PROGNOSIS: good, but females at risk of hypoglycemia during pregnancy

22
Q

GSD V (McArdle)

  • deficiency in what?
  • genetics
A

myophosphorylase deficiency

PYGM gene on chromosome 12q13

23
Q

GSD V (McArdle) symptoms

A

child-onset exercise intolerance

brief exertion may cause muscle cramps, myoglobinuria, hyperuricemia, mild CPK elevation

24
Q

GSD V (McArdle)

  • diagnosis
  • treatment
  • prognosis
A

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

25
Q

GSD VII (Tarui) etiology

A

muscle phosphofructokinase deficiency
PFKM gene on chrom 11
prevalent in Japanese and Ashkenazim

26
Q

GSD VII (Tarui) symptoms

A

child-onset exercise intolerance
brief exertion may cause muscle cramps, myoglobinuria, hyperuricemia, mild CPK elevation

compensated hemolysis

27
Q

GSD VII (Tarui)

  • diagnosis
  • treatment
  • prognosis
A

DIAGNOSIS

  • bicycle/treadmill test to detect increased uric acid and ammonia
  • if treadmill test is abnormal, enzyme assay

TREATMENT
- avoid strenuous exercise

PROGNOSIS: good

28
Q

AMPK deficiency: gene and inheritance

A

PRKAG2 on chr 7

AD, full penetrance

29
Q

AMPK deficiency: symptoms

A

onset typically late adolescence

cardiac symptoms including hypertrophy, familial hypertrophic cardiomyopathy with WPW syndrome

30
Q

AMPK deficiency:

  • diagnosis
  • treatment
  • differential diagnoses
A

DIAGNOSIS:

  • ECG
  • heart biopsy
  • molecular genetics

TREATMENT

  • pacemaker/defibrillator
  • heart transplant

DDx: Pompe, Danon, Fabry

31
Q

Lafora Disease etiology

A

mutations in Laforin-malin complex, which brings glycogen synthase from neurons to proteosome for glycogen breakdown

  • accumulation of branched chain glycogen
  • triggers neuronal apoptosis

EPM2A encodes laforin
EPM2B encodes malin

32
Q

Lafora Disease symptoms

A

adolescent onset of myoclonic epilepsy and absence seizures
progressing to dementia with visual loss, apraxia, and aphasia
ultimately leads to vegetative state

33
Q

Lafora disease:

  • diagnosis
  • treatment
  • prognosis
A

DIAGNOSIS

  • skin biopsy to detect Lafora bodies
  • mutation analysis to confirm

TREATMENT: none

Poor prognosis, death within decade of disease onset

MedGen 2 (13 decks)

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