Clinical applications of Carbohydrates Flashcards
Glycogen Storage Disease (GSD) von Gierke (Ia), Cori (III), Andersen (IV)
Von Gierke (Type Ia)
–_________________deficiency
–Accumulation of _________
–Neonate or in first 12 months
–Profound hypoglycemia, subnormal response to __________
–Risk __________ brain damage in early infancy
Cori (Type III)
–Milder form of type I
–________________enzyme deficiency
–Intact____________
Andersen (Type IV)
–____________ enzyme deficiency
–Progressive ____________disease
–Hydrops fetalis
Glucose-6-phosphatase (G6P)
glycogen
glucagon
hypoglycemic
Debranching
gluconeogenesis
Branching
liver
Lab Findings Classic Galactosemia
Abnormal ________ metabolism
–Increased plasma ___________and RBC____________ concentration
–Increased blood and urine __________ levels
Liver dysfunction
–Conjugated (direct/water soluble) __________
–Abnormal liver function tests (increased AST and ALT)
–Coagulopathy due to loss of _____________with loss of liver function
–Increased plasma amino acids (especially __________, ____________, and __________
)
Renal tubular dysfunction
–Metabolic acidosis
–Galactosuria (reducing substances in the urine)
–Glycosuria
–Aminoaciduria
–Albuminuria
Hemolytic anemia
carbohydrate
galactose
galactose-1-phosphate
galactitol
hyperbilirubinemia
clotting factors
phenylalanine, tyrosine, and methionine
Cataracts
May present a few days after birth in Types I & II GS
Classic ‘Oil drop cataract’ oil droplet silhouetted against the red reflex
–Rapid vision loss possible
–Rapid unexplained, myopic progression with concomitant diplopia
Mechanism
–High ___________ in lens triggers aldose reductase to convert __________ to ________
–Lens membranes relatively ______ to sugar alcohols
–Galactitol once formed accumulates creating a __________state –To maintain osmotic equilibrium, water drawn into the lens fibers resulting in osmotic ___________ & electrolyte _______
–Aldose reductase inhibitor, __________, promising in preventing and reversing galactosemic cataracts
galactose
galactose; galactitol
impermeable
hypertonic
swelling; imbalance
sorbinil
Essential Fructosuria
Autosomal recessive inheritance
–Clinically benign symptomatic
–Fructose not trapped in cells
Deficiency of __________________
–Catalyzes the first step of metabolism of dietary fructose, conversion of ______________ to __________
–Present in both liver and pancreatic islets
Unable to break down fructose: fructose in _________& _________
–Increased urine reducing substances
fructokinase AKA ketohexokinase (KHK)
fructose; fructose-1-phosphate
urine ; blood
Presymptomatic IEM Newborn Screening (NBS)
When is important to treat?
Is brain damage reversible with therapy?
Abnormal __________ identified in newborn
Tandem mass spectrometry (MS/MS)
Multiple analytes detected and quantified simultaneously
In US NBS, >4 million infants screened annually
Hearing: hearing loss screen <1 month of age
BEFORE symptoms appear
No
metabolites
Inborn Errors of Metabolism (IEM)
Collective incidence: 1:800 to 1:2500
Individual disease rare: <1:100,000
Most common: __________ 1:12,000
___________ mutation with large effect
–In enzyme controlling rate of chemical reaction
Majority familial
Mendelian inheritance
–Autosomal recessive (most)
When is recessive phenotype expressed?
–X-linked recessive (rare)
Systemic effects (most)
Presentation at a young age
Complete penetrance
phenylketonuria
Single gene
only when both chromosomes of a pair carry mutant alleles
Morbidity and Mortality in IEM
Excess toxic_________ or substrate proximal to metabolic block
–e.g., galactitol in classic ____________
Byproducts not normally present
–e.g., phenylpyruvic acid in ___________
Lack of product(s) or end-product distal to enzyme block
–e.g. albinism
metabolite
galactosemia
phenylketonuria
Classic Presentation of IEM in Infancy
Acute metabolic ___________with __________-induced vomiting, neurologic dysfunction, hyperammonemia
–_________ cycle defects, organic acidemias
Progressive neurologic deterioration
–Phenylketonuria (PKU)
Silent until body requires_________from fat during infections, fever, fasting
–__________disorders
encephalopathy; protein
Urea
energy
Fatty acid oxidation
Classic Galactosemia
Clinical Presentation
Present in first few days of life
–After initiation of _________containing human breast milk or cow’s milk-based feedings
Failure to thrive from birth
__________ due to accumulation of lipid (fat)
Cholestatic ____________
Poor feeding
Diarrhea
Sepsis
Infantile cataracts (usually few weeks after birth)
galactose
Hepatomegaly
jaundice (increased bilirubin)
Classic Presentation of Carbohydrate Disorder in Infancy
Hepatomegaly and liver failure + jaundice + cataracts
–Classic Galactosemia (Type I) is known as ___________
Hepatomegaly and liver failure
–Hereditary _________ Intolerance
- __________________deficiency
Hypoglycemia with hepatomegaly
–____________storage disease Type Ia von Gierke
- __________ deficiency
- Hepatic adenoma/hepatocellular carcinoma, renal failure with hypertension
Cardiomegaly (hypertrophic cardiomyopathy)
–Glycogen storage disease type II Pompe (early onset)
- _________________deficiency
- Heart failure and respiratory insufficiency
galactose-1-phosphate uridyl transferase (GALT)
Fructose
fructose-1-phosphate aldolase (fructoaldolase B)
Glycogen
glucose 6-phosphatase
lysosomal acid maltase/acid α-glucosidase
Hereditary Fructose Intolerance (HFI)
Autosomal recessive inheritance
Deficiency of ________________
–In liver, kidney, and intestinal mucosa
_____________ accumulation
–Damages liver, kidney, and brain
–Inhibits ______________and ___________
–Resulting in _____________, ___________, and _____________
Recurrent hypoglycemia and vomiting at weaning from breast milk
–Fructose or sucrose (disaccharide hydrolyzed to glucose and fructose) added to infant’s diet
Hepatomegaly, jaundice, coagulopathy
–Steatosis and giant cell transformation (similar to galactosemia lesions)
–Portal septal fibrosis, ductular proliferation, cholestasis
Renal failure with renal tubular acidosis, aminoaciduria, proteinuria
fructose-1-phosphate aldolase (fructoaldolase B)
Fructose -1-phosphate
glycogenolysis ;gluconeogenesis
hypoglycemia, phosphate sequestration, ATP depletion
Classic Galactosemia
Proteinuria and aminoaciduria due to
–Impaired ___________ transport
Indirect _____________ due to
–Hemolysis due to high levels of ____________ in RBCs
Increased incidence of Escherichia coli sepsis
–Galactose depresses _________ bactericidal activity
Intellectual disability
–By 6-12 months, if untreated, death
amino acid
hyperbilirubinemia
galactose-1-phosphate
neutrophil
Classic Galactosemia
Physical and Pathologic Findings
____________due to fat
Yellow tawny _________ due to excess fat in liver cells (steatosis)
Cataracts (lens opacification)
Brain
–Dentate nuclei in cerebellum
–Olivary nuclei in medulla
–Cerebral cortex, white matter
–Nerve cell loss
–Gliosis
–Edema
Hepatomegaly
liver
Galactosemia (GS)
Enzyme Deficiency Types
Galactose-1-phosphate uridyl transferase (GALT) deficiency
–Most common and severe form if complete GALT deficiency (classic Type I)
–GALT converts _______________ to______________
Galactokinase (GALK) deficiency
–GALK 1st enzyme in galactose metabolism, converting __________ to _____________
–Only consequence development of ___________
Uridine diphosphate (UDP) galactose 4-epimerase (GALE) deficiency
–UDP GALE converts _________ to ___________
–In most, defect localized to ____________, normal growth/development
galactose-1-phosphate; uridine diphosphate galactose (UDP-galactose)
galactose; galactose-1-P
cataracts
UDP-galactose; UDP-glucose
red blood cells (RBCs)
Management Galactosemia
Immediate dietary intervention
Minimize dietary ___________ by excluding breast and cow’s milk and other dairy products from the diet
If galactose elimination soon after birth
–Prevention of __________
–Elimination of ________ damage
In infants, human milk or formula based on bovine milk discontinued and a soy-based formula given
galactose
cataracts; liver
