Question 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

Accepted Answer

Glucose-6-phosphatase (G6P) glycogen glucagon hypoglycemic Debranching gluconeogenesis Branching liver

Question 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

Accepted Answer

carbohydrate galactose galactose-1-phosphate galactitol hyperbilirubinemia clotting factors phenylalanine, tyrosine, and methionine

Question 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

Accepted Answer

galactose galactose; galactitol impermeable hypertonic swelling; imbalance sorbinil

Question 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

Accepted Answer

fructokinase AKA ketohexokinase (KHK) fructose; fructose-1-phosphate urine ; blood

Question 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

Accepted Answer

BEFORE symptoms appear No metabolites

Question 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

Accepted Answer

phenylketonuria Single gene only when both chromosomes of a pair carry mutant alleles

Question 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

Accepted Answer

metabolite galactosemia phenylketonuria

Question 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

Accepted Answer

encephalopathy; protein Urea energy Fatty acid oxidation

Question 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)

Accepted Answer

galactose Hepatomegaly jaundice (increased bilirubin)

Question 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

Accepted Answer

galactose-1-phosphate uridyl transferase (GALT) Fructose fructose-1-phosphate aldolase (fructoaldolase B) Glycogen glucose 6-phosphatase lysosomal acid maltase/acid α-glucosidase

Question 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

Accepted Answer

fructose-1-phosphate aldolase (fructoaldolase B) Fructose -1-phosphate glycogenolysis ;gluconeogenesis hypoglycemia, phosphate sequestration, ATP depletion

Question 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

Accepted Answer

amino acid hyperbilirubinemia galactose-1-phosphate neutrophil

Question 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

Accepted Answer

Hepatomegaly liver

Question 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

Accepted Answer

galactose-1-phosphate; uridine diphosphate galactose (UDP-galactose) galactose; galactose-1-P cataracts UDP-galactose; UDP-glucose red blood cells (RBCs)

Question 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

Accepted Answer

galactose cataracts; liver

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Clinical applications of Carbohydrates Flashcards

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