Biochem Part III - Metabolism Disorders

Question 1

Fructose intolerance? leads to what physiologlically? Sx?Tx?

Answer 1

A/R. Decrease in Aldolase. Leads to elevated fructose 1 phosphate levels and decreased availability of phosphate that inhibits glycogenolysis and gluconeogenesis.Symptoms present after eating fruit, juice or honey. Sx: jaundice, cirrhosis, hypoglyemia, vomiting. TX: decrease intake of both fructose and sucrose (glucose + fructose)

Question 2

Galactokinase deficiency. Inheritance? Xs?

Answer 2

A/R. Unable to convert galactose to galactose 1P. Galactose gets converted to galactilol instead by aldose reductase. Galactilol accumulates. Sx: galactose appears in blood and urine. Infantile cataracts. May present as failure to track objects or develop a social smile.

Question 3

Classic galactosemia. Sx? Can lead to what in neonates. When do sx appear in neonates?

Answer 3

A/R. Absence of galactose 1 phosphate uridyltransferase. Inability to convert Galactose 1 P to Glucose 1P. Sx: Failure to thrive, cataracts, jaundice, hepatomegaly, intellectual disability. Tx: exclude galactose and lactose (glucose and galactose) from diet. Can lead to E coli sepsis in neonates. appears after breastfeeding is initiated.

Question 4

What reactions does aldose reductase catalyze

Answer 4

1) Galactose to galactilol and 2) glucose to sorbitol

Question 5

What cells have both aldose reductase and sorbitol dehydrogenase. What cofactor? does it need

Answer 5

Liver, ovaries, seminal vesicles. Glucose to sorbitol (using aldose reductase) to fructose (using sorbitol dehydrogenase). Both reactions require NADPH

Question 6

What cells have only aldose reductase

Answer 6

Lens, schwann cells, retina kidney

Question 7

Ornithine transcarbamylase deficieny inheritance and ppt?

Answer 7

X linked recessive. Most common urea cycle disorder. Excess carbamoyl phosphate is converted to orotic acid => orotic aciduria except NO megalobastic anemia. Other findings: increased orotic acid in blood/urine, decreased BUN/sx of hyperammonemia.

Question 8

Ornithine transcarbamylase deficieny inheritance and ppt?

Answer 8

X linked recessive. Most common urea cycle disorder. Excess carbamoyl phosphate is converted to orotic acid => orotic aciduria except NO megalobastic anemia. Other findings: increased orotic acid in blood/urine, decreased BUN/sx of hyperammonemia.

Question 9

What is the pathobiology of PKU. Inheritance? Tx? Dietary restrictions?

Answer 9

A/R. Screened for 2-3 days after birth (normal at birth because of maternal enzyme during fetal life). Decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor (malignant PKU). Tyrsoine becomes essential. Increased phenyalanines leads to phenylketons in urine. Findings: intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor. Tx: decreased phenylalanine and increased tyrosine in diet. Avoid artificial sweetener like aspartame that has phenylalanine

Question 10

What is alkaptonuria? Inheritance? Sx?

Answer 10

AKA ochronosis. A/R. Benign. Deficiency in homogentisate oxidase which is necessary in the degradation of tyrosine/Phe to fumarate. URINE TURNS BLACK ON PROLONGED AIR EXPOSURE. Results in the accumulation of homogentisate in cartilage (ears),sclera dermis and skin and also excreted in urine/sweat. Homogentisate is toxic to cartilage and may cause bad arthralgias

Question 11

How do patients with homocystinuria present? What are they at risk for?

Answer 11

Elevated homocystine in urine, intellectual disability, Lens subluxation/ectopia lentis (dislocated lens), marfinoid habitus (long limbs, arachnodactyly), osteporosis. High risk for thromboembolic episodes involving large and small vessel especially in brain heart and kidney

Question 12

Most common cause of homocystinuria

Answer 12

deficiency of cystathione synthetase, requires Vit B6 (pyridoxine). Treat with Vit B6, 50% of patients respond well

Question 13

What is cystinuria. Diagnosis / Tx

Answer 13

Hereditary defect in renal PCT and intestinal amino acid transporter for COLA (cysteine, ornithine, lysine and arginine). Excess cysteine in urine leads to cystine stones (2 cysteines connected by disulfide bond). TX: urinary alkalinazation (Acetazolamide, potassium citrate), chelating agents increase cystine stone solubility, good hydration. Urinary cyanide-nitroprusside test is diagnostic.

Question 14

What is maple syrup urine disease? Inheritance? Sx? Tx?

Answer 14

A/R. Defect in the breakdown of branched chain amino acids due to defect in alpha ketoacid dehydrogenase. Normally gets broken down to acetyl coA but can’t and tissue and serum levels of alpha-ketoacids begin to rise which leads to neurotoxicity. SX: Urine smells like maple syrup. Severe CNS defects, intellectual disability, death TX: thiamine supplementation, restriction of leucine, isoleucine, leucine.

Question 15

What are the branched chain amino acids?

Answer 15

Leucine, isoleucine and valine

Question 16

What are the glycogen storage disorders. Mnemonic?

Answer 16

Very Poor Carboyhydrate Metabolism. Von gierke, Pompe, Cori, McArdle

Question 17

What is Von Gierke’s Disease? Inheritance? Findings? Tx?

Answer 17

A/R Type 1 glycogen storage disease. Deficient enzyme = glucose 6 phosphatase (remember, not present in muscle). FINDINGS: Severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly TX: frequent oral glucose/cornstarch; avoidance of fructose and glucose

Question 18

What is Pompe Disease? Inheritance? Findings? Tx?

Answer 18

A/R. Type 2 glycogen storage disease. Deficient enzyme = lysosomal alpha 1-4 glucosidase. This enzyme degrades glycogen. Findings: cardiomyopathy and systemic findings lead to early death. Glycogen accumulation in lysosomes. Normal blood sugar. POMPE trashes the PUMP (heart, liver, muscle)

Question 19

What is Cori Disease? Inheritance? Findings? Tx?

Answer 19

A/R Type 3 glyocgen storage disesase. Deficient enzyme = debranching enzyme (alpha 1,6 glucosidase). FINDINGS: milder form of type 1 with normal blood lactate levels. Accumulation of short dextrin molecules and no fatty infiltration of the liver. Gluconeogenesis is intact.

Question 20

What is McArdle Disease? Inheritance? Findings? Tx?

Answer 20

A/R Type 5 glycogen storage disease. Deficient enzyme = skeletal muscle glycogen phosphorylase. Findings: increased glycogen in muscle without ability to break it down = painful cramps. Myoglobinuria (with strenous exercise) and arrhythmias in exercise due to electrolyte balances

Question 21

What are the two main categories of lysosomal storage diseases

Answer 21

Sphingolipidoses and mucopolysaccharidoses

Question 22

Which of the lysosomal storage diseases are XR inheritance?

Answer 22

Fabry disease and Hunter Syndrome

Question 23

Mnemonic for sphingolipidoses

Answer 23

Four Guys Need Their Krabbe Mitts. Fabry disease, Gaucher disease, Nieman Pick disease, Tay Sachs, Krabbe disease, Metachromatic leukodystrophy

Question 24

What is Fabry disease? Inheritance? Deficient Enzyme? Accumulated Substrate? Findings?

Answer 24

Lysosomal storage disease. X linked recessive. Deficiency in alpha-galactosidase A. Leads to accumulation of ceramide trihexoside. PPT: peripheral neuropathy, angiokeratomas. Leads to progressive cardiovascular, renal disease

Question 25

What is Gaucher disease? Inheritance? Deficient Enzyme? Accumulated Substrate? Findings? Tx

Answer 25

Lysosomal storage disesase. AR. Most common. Deficient in glucocerebrosidase (beta glucosidase) leading to accumulation of glucocerebroside. Findings: Hepatosplenomegaly, pancytopenia, necrosis of femur, bone crises, Gaucher cells (lipid laden macrophages resemble crumpled tissue paper). Tx: recombinant glucocerebrosidase

Question 26

Describe Niemann-Pick Disease. Inheritance? Accumulated substrate? Presentation?

Answer 26

A/R disorder that presents in infants of Ashkenazi jews. Deficiency of sphingomyelinase that causes sphingomyelin to accumulate within phagocytes. Resultant foamy histiocytes accumulate in the liver, spleen and skin. Hepatosplenomegaly. Gradual sphingomyelin deposition in the CNS causing neurologic degeneration. Loss of previously acquired motor skills Progresses to hypotonia and blindness. Cherry red macular spot (like in Tay Sachs)

Question 27

Tay Sachs Disease? Inheritance? Accumulated Substrate? Characteristics?

Answer 27

A/R. Defect in beta hexosamindase A. Results in accumulation of GM2 ganglioside. Normal development till around 2-6 months then you start getting hyptonia, progressive weakness, loss of motor skills. PPT: Cherry red spot in macula, progression neurodegeneration (startle reflex), NO hepatosplenomegaly unlike Niemann Pick disease.

Question 28

Krabbe Disease? Inheritance? Accumulated Substrate? Characteristics?

Answer 28

A/R. Deficiency in galactocerebrosidase leading to accumulation of galactocerebroside and psychosine. Findings: Peripheral neuropathy, developmental delay, optic neuropathy, globoid cells.

Question 29

Metachromatic leukodystrophy? Inheritance? Accumulated Substrate? Characteristics?

Answer 29

A/R. Deficiency in aryslsulfatase A. Accumulated substrate is cerebroside sulfate. Findings: Central and peripheral demyelination with ataxia, dementia.

Question 30

What is Hurler Syndrome? Deficient enzyme? Accumulatd substrate? Findings?

Answer 30

A/R. Deficiency in alpha L iduronidase. Accumulation of heparin sulfate and dermatan sulfate. Findings: developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly.

Question 31

What is Hunter Syndrome? Deficient enzyme? Accumulatd substrate? Findings?

Answer 31

X/R. Deficiency in iduronate sulfatase. Accumulatino of heparin sulfate and dermatan sulfate. Findings: mild hurler and aggressive behanvior, no corneal clouding

Question 32

Acetyl CoA is an allosteric regulator of what?

Answer 32

Pyruvate carboxylate in gluconeogenesis.

Question 33

What is Acyl CoA dehydrogenase deficiency? Findings?

Answer 33

Needed for conversion of acyl CoA into ultimately acetyl CoA that can be used to generate ketones or enter the TCA. Deficiency leads to increase in dicarboxylyic acids, decreased glucose (esp fasting glucose) and ketones

Question 34

What is carnitine deficiency? PPT

Answer 34

Results in inability to transport long chain fatty acids into the mitochondria. Resulting in toxic accumulation. Causes weakness, hypotonia, hypoketotic hypoglycemia.