Clinical applications of Carbohydrates Flashcards Preview

Molecules and Cells (Unit 1) > Clinical applications of Carbohydrates > Flashcards

Flashcards in Clinical applications of Carbohydrates Deck (18):
1

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

2

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

3

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

4

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

5

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

6

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

7

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

8

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

9

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)

10

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

 

 

11

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

12

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

13

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

14

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)

15

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

16

Clinical Manifestations IEM

Most common: neurologic & gastrointestinal

Acute signs

–Episodic vomiting with __________or shock

–Lethargy and coma

–__________with stress or prolonged fast

Chronic signs

–Growth delay/failure to thrive

–___________

–Cardiomegaly/Cardiomyopathy

–Developmental delay

Dehydration

Hypoglycemia

Hepatomegaly

17

Classic Galactosemia (GS)

__________ recessive inheritance

Also known as Galactosemia Type I

NBS in all states in US (& DC) test for galactosemia

Absence of _____________

Can’t break down _______

–In human breast milk or cow’s milk

Toxic accumulating substances:

_____________

______________

______________

Greatest damage: __________,_________,_________

 

Autosomal

galactose-1-phosphate uridyl transferase (GALT)

galactose

–Galactose-1-phosphate

–Galactitol (polyol metabolite)

–Galactonate/galactonic acid (oxidized byproduct)

liver, cerebral cortex, RBCs

18

When to Suspect a Metabolic Disease

Positive family history

____________ parents (same ancestor)

–Confined ethnic or geographic background

–Amish in Pennsylvania

–Eastern European (Ashkenazi) Jews

–Country with little immigration (Finland)

Second child affected

Acute unexplained death in older sibling

“__________ with unknown pathogen”

“Encephalopathy”

“Sudden Infant Death Syndrome”

Consanguineous

Sepsis