Exam 2 Diseases

Question 1

Glycation/fructation

Answer 1

(Maillard reaction); a reaction between a protein and a reducing sugar where the -OH attach the amino end of a protein; seen in browning of meat, toast, etc when cooking. Important because in diabetics, the surface proteins are exposed to high levels of glucose which leads to advanced modification of proteins like Hb, leads to high cross linkage. These accumulate over the half-life of the molecule and those structures have a different mobility on electrophoretic gel than normal Hb- basis of HbA1C test (normal value ~5%, but can be as high as 13%) gives picture of Hb’s exposure to sugar over the base 2-3 months

Question 2

Lactase deficiency

Answer 2

• leads to indigestion of lactose until the large intestine where bacteria digest it and leads to production of CO2 and byproducts that draw in water leading to gas and diarrhea. Note: lactase deficiency is the wild type because after infancy, there is no need for lactose until recently where milk from other animals was consumed

Question 3

cholera

Answer 3

• SGLT1 is a transporter in the lumenal side of the small intestine that imports glucose and galactose with Na+; in cholera, efflux of Cl- leads to efflux of glucose/Na+ because Na+ follows Cl-, but people found that if water mixed with glucose and salt is administered, it can lead to rehydration because the difference in intracellular and extracellular Na+ concentration overpowers the attractive charge of the Cl- leaving the cell- known as oral rehydration therapy

Question 4

Carboxylase deficiencies

Answer 4

Biotin is used in pyruvate, acetyl coA and propionyl coA carboxylase enzymes and leads to lactate and acetyl-coA and ketone accumulation, FA synthesis failure, developmental retardation, hallucinations, leathery, and rash. Deficiency can be due to dietary deficiency or metabolic deficiency in attachment or absorption of biotin in the diet. Can be treated with excess dietary biotin

Question 5

Cori disease

Answer 5

Type III: Cori disease- deficiency in deb ranching enzyme in the muscle and liver leading to similar, but more mild symptoms of von Gierke disease.

Question 6

Andersen disease

Answer 6

Tyie IV: Andersen disease- branching enzyme deficiency affecting the liver and heart muscle. Leads to death from liver cirrhosis before age 2

Question 7

Hers disease

Answer 7

Type VI: Hers disease- glycogen phosphorylase deficiency in the liver leading to less severe symptoms from type I (von Gierke) with milder hypoglycemia

Question 8

Tauri disease

Answer 8

Type VII: Tauri disease- phosphofructokinase deficiency in the liver and RBCs leading to similar presentation as type V

Question 9

Type VIII glycogen storage disease

Answer 9

Type VIII: phosphorylase kinase deficiency of the liver leading to mild hepatomegaly and mild hypoglycemia

Question 10

Type IX glycogen storage disease

Answer 10

Type IX: glycogen phosphorylase kinase deficiency

Question 11

Type XI Glycogen storage disease

Answer 11

Type XI: GLUT2 transporter deficiency, Franconi-Bickel

Question 12

Excess fructose

Answer 12

• can lead to F1P accumulation due to fructose pathway bypassing rate limiting PFK1 step and aldolase B being slower than fructokinase due to it preferring F1,6BP as a substrate. F1P activates GRP, but has no affect on PFK, so stimulates glycogen synthesis, but also ties up a large amount of inorganic phosphate. The increased glycogen levels can also lead to shunting of glucose and fructose to lactic acid and FA production over time, possibly leading to accumulation of lipids in the liver if VLDLs can’t handle the FA load; this leads to FA liver disease
• Note; fructose cannot be converted to G6P, so it can’t enter the pentose phosphate pathway or glycolysis, so it is converted to fat when in excess in the liver. (In other tissues, hexokinase is used so it can be used like glucose, but other tissues only metabolize 10% of fructose).

Question 13

Essential fructosuria

Answer 13

low levels of fructose in the urine due to fructokinase deficiency (liver); most of the fructose after a meal is broken down slowly by hexokinase; benign disease

Question 14

Hereditary fructose intolerance

Answer 14

autosomal recessive aldolase B deficiency. Leads to vomiting and nausea after a fructose containing meal with weakness trembling and sweating (signs of hypoglycemia). F1P builds up in the liver leading to shortage of phosphate for ATP synthesis; this causes damage to the cells and impairs gluconeogenesis and glycogenolysis; can destroy the liver in days. Defiencncy in F16BPase leads to similar state but with actual hypoglycemia because gluconeogenesis is impoaired. This leads to conditioned taste aversion for sweet things. Note: aldolase B is major hepatic form, but in other tissues other isoforms are also present so glycolysis is not affected: aldolase A can work on glucose, but not on fructose

Question 15

Galactokinase deficiency

Answer 15

mildly elevated blood galactose levels, but can develop cataracts if galactose consumption is continued due to aldolase reductase (converts glucose to sorbitol) converting galactose to galactitol in the lens

Question 16

Galactose-1-phosphate uridyl transferase deficiency

Answer 16

galactosemia; consumption of milk leads to elevated blood gal levels and Gal1P accumulation in cells. After eating/drinking milk products, individuals start vomiting weeks after birth, can lead to cataracts, liver cirrhosis, and mental deficiencies. Due to shortage of phosphates being tied up as Gal1P; leads to liver cell death. Diagnosed with urine test for reducing sugar and subsequent negative test for glucose. Treatment is early diagnosis and implementation of milk free diet.

Question 17

Heinz bodies

Answer 17

• Oxidative stress in RBCs from H2O2 and O2- can lead to denatured Hb called Heinz bodies that lead to RBC lysis; leads to hemolytic anemia

Question 18

G6PDH deficiency

Answer 18

the most common deficiency in humans known. It is X-linked; and there are 400 different mutations known that decrease ability to deal with oxidative stress through less active or less stable enzyme. RBCs most affected. This confers resistance to malaria, so it persists (malaria doesn’t like oxidative environments, so increased oxidative stress in RBCs repels malaria).

Question 19

chronic granulomatous disease (CGD)

Answer 19

Some microorganisms have catalase and SOD, so are resistant to these mechanisms and the bodys only defense is HOCl; so deficiency in G6PDH can lead to chronic granulomatous disease (CGD) from excessive granuloma formation in response to infections

Question 20

Favism

Answer 20

• RBCs are unable to handle the oxidative stress due to some drugs or food items (e.g.. fave beans). People who have levels on the brink of normal can be pushed over the edge by these oxidative foods and can die from exposure to these foods and drugs. Favism is the name for this condition of oxidative stress brought on by food/drugs.

Question 21

Neonatal jaundice

Answer 21

can be due to many reasons, possibly due to inability of mature liver to process bilirubin which is a neurotoxin; kernicterus is bilirubin accumulation in the grey matter. Treated bu “bili-lights that converts bilirubin to water soluble photo isomer lumirubin which cannot enter the CNS and is excreted quickly

Question 22

anion gap

Answer 22

• The anion gap refers to the difference between the measured anions and the measured cations in the serum. In normal serum, there are more measurable cations than anions, so the gap is positive. The gap constitutes the unmeasured anions including plasma proteins. The anion gap is calculated by taking the sum in molarity of the cations and subtracting the concentrations of the anions. It is used to diagnose metabolic acidosis*
  
  • usually about 12mEq/L +/-4mEq/L. If exogenous acid is present, then the anion gap increases indicating metabolic acidosis
  • Calculated by subtracting the concentration of Cl- and bicarbonate from the concentration of Na+ and the other ions are ignored to facilitate a rapid diagnosis

Question 23

blood pH CNS involvement

Answer 23

• Alkalosis can lead to H+ diffusing out of the cell and K+ diffusing in, depolarizing the membrane and leading to over-stimulation; causes spasms, tetany, convulsions, and respiratory paralysis.
• Acidosis can lead to H+ entering cells and driving out K+, leading to hyperpolarization of the membranes and causing CNS depression that can lead to death.

Question 24

Metabolic acidosis etiology

Answer 24

• ELMPARK; can determine the cause depending on the anion that is elevated
  
  • Anon elevated: Etiology
  • Glyoxylate. Ethylene glycol
  • Lactic acid. Lactic acidosis
  • Formic acid. Methanol
  • Acetaldehyde. Paraldehyde
  • Salicylate/lactate. Aspirin
  • Sulfate/phosphate. renal tubular acidosis (will have normal anion gap) and uremia (inability to excrete ammonia)
  • Butyrate/acetoacetate ketoacidosis

Question 25

Common values for blood

Answer 25

• Arterial pH: 7.35-7.45
• Veinous pH: 7.32-7.42
• Arterial PO2: 80-100 mm
• Veinous Po2: 28-48 mm
• Arterial HCO3: 22-26 mEq
• Veinous HCO3: 19-25 mEq
• Arterial PCO2: 35-45 mm
• Veinous PCO2: 38-52 mm

Question 26

beriberi

Answer 26

Deficiency in Vitamin B1

• Can be due to dietary insufficiency, hyperthyroidism, lactation/pregnancy, diarrhea, etc.
• Symptoms include fatigue, irritability, sleep disturbances, anorexia, chest pains, abdominal pain, and constipation
• Results in accumulation of pyruvate, lactate, citrate, and α-ketoglutarate

Question 27

ethanol “poisoning”

Answer 27

• Converted to acetaldehyde tough alcohol dehydrogenase yielding NADH
• Acetaldehyde is converted to acetate in the mitochondria through acetaldehyde DH giving NADH
• This process gives a lot of NADH, so pyruvate is converted to lactate to give NAD+ through lactate DH, but in the fasted state, pyruvate is needed, so excessive drinking can lead to mild hypoglycemia because the accumulation of NADH in the mitochondria inhibits NADH shuttling to the mitochondria, leading to an increase in cytosolic NADH
• If too much NADH is accumulated, the second reaction involving the conversion of acetaldehyde is unable to proceed and acetaldehyde is responsible for the hangover through the formation of adducts with proteins and nucleic acids. Eventually resolves due to ETC use of NADH to regenerate NAD+
• NAD+ accumulation also inhibits gluconeogenesis because NAD+ is needed to oxidize lactate to pyruvate
• The final product of this, acetate, is converted to acetyl-coA and is used to synthesize fats. Chronic production of acetyl-coA leads to “fatty liver” seen in alcoholics

Question 28

High fructose diet

Answer 28

Fructose can deplete the liver of ATP/Pi due to overload of aldolase B, (this tying up of the inorganic phosphate can lead to inhibition of phosphorylysis of glycogen to glucose, leading to hypoglycemia- debated) so can lead to uric acid production because it tries to get inorganic phosphate thorough breakdown of nucleic acids, leading to hyperuricemia (gout); this can also be seen in chemotherapy, so needs to be treated with allopurinol with the chemo. Uric acid also inhibits NO synthase, leading to hypertension.

Question 29

von Gierke disease

Answer 29

• Hepatic: Type I glycogen storage disease
• Deficiency in glucose-6-phosphatase
• Leads to:
  
  • Hepatomegaly; intracytoplasmic and intranuclear accumulation of glycogen and small amounts of lipid
  • Renomegaly: intracytoplasmic accumulation of glycogen in the cortical tubular epithelial cells
• Clinical features:
  
  • Failure to thrive, stunted growth, hepatomegaly, and renomegaly in untreated patients
  • Hypoglycemia due to failure in glucose mobilization; can lead to convulsions
  • Hyperlipidemia and hyperuricemia due to faulty glucose metabolism. Some patients develop gout and skin xanthomas
  • Bleeding tendency caused by platelet disfunction
  • With treatment (continuous source of glucose), most patients survive and develop late complications (e.g. hepatic adenomas)

Question 30

McArdle disease

Answer 30

• Myopathic: Type V glycogen storage disease
• Deficiency in muscle glycogen phosphorylase
• Leads to:
  
  • Accumulation of glycogen in skeletal muscles only
  • Predominant in subsarcolemmal location
• Clinical features:
  
  • Painful cramps when exercising
  • Myoglobinuria in 50% of cases
  • Onset in adulthood (>20 year)
  • Muscle exercise fails t increase lactate level in blood
  • Compatible with normal longevity (normal lifespan)

Question 31

Pompe disease

Answer 31

• Type II glycogen storage disease
  * Also a lysosomal storage disease
  * Deficiency in lysosomal glucosidase (acid maltase: A small amount of glycogen is continuously degraded in the lysosomes. By the lysosomal enzyme α-1,4-glucosidase (acid maltase). The significance of this pathway is unknown. However, a deficiency of this enzyme cause accumulation of glycogen in the cytosol. Results in glycogen storage disease type I-Pompe’s disease)
  * Leads to:
  * Mild hepatomegaly; ballooning of lysosomes
  * Cardiomegaly: glycogen in the sarcoplasms as well as membrane bound glycogen
  * Skeletal muscle has similar pathology to the heart
  * Clinical features:
  * Massive cardiomegaly, muscle hypertonia, and cardiorespiratory failure by age 2
  * Milder adult form with only skeletal muscle involvements manifests with chronic myopathy
  * Early recognition is critical because treatment with recombinant enzyme Myozyme (alglucosidase α) supplementation can allow survival through infancy. Must be given via IV biweekly. Complications can arise if the infant produces no enzyme; will recognize the enzyme as foreign and attack it. If they are at risk for this complication, must also be given immune modification treatment with Myozyme

Question 32

X-linked adrenoleukodystrophy (ALD)

Answer 32

inherited demyelination disease due to defect in import of VLCFAs into peroxisomes. Caused by defects in ABCD1 gene and peroxisomal VLCFA coA transporter. Symptoms include weakness and stiffness in legs, impaired visoion, and behavioral problems. Females with one mutation on one of their X chromosomes may exhibit adrenomyeloneuropathy (AMN) rather than ALD in middle age. This leads to progressive neuropathy, paraparesis (loss of motor function), and adrenal insufficiency.

Question 33

Adult Refsum disease (ARD)

Answer 33

humans obtain phytanic acid (derivative of chlorophyll; branched chain FA (BCFA)) from their diet; must be broken down by α oxidation because methyl group prevents β oxidation. It is the only substrate of α oxidation which uses phytanoyl CoA carboxylase as one of the enzymes. Deficiency causes ARD, leading to accumulation of phytanoic acid. It is an autosomal recessive neurologic disease which h leads to polyneuropathy, cerebellar taxis, retinas pigmentosa, anosmia, and hearing loss

Question 34

Infantile refsum disease

Answer 34

Infantile refsum disease is an autosomal recessive deficiency in the PEX genes and falls into the Zellweger spectrum disorders. Causes cerebral demyelination and loss of hearing and vision

Question 35

MCAD deficiency

Answer 35

leads to shunting of products to ω oxidation; normally a minor pathway, but generates dicarboxylic FAs. These dicarboxylic FAs can be detected in plasma and urine.

Question 36

Type I diabetes

Answer 36

• starts in childhood or adolescence and is an autoimmune disease where the β cells of the pancreas are destroyed by the immense system
  
  • Causes lack of insulin activity and dependence on insulin injections
  • Incidence of abut 1/400; does not correlate to lifestyle

Question 37

Type II diabetes

Answer 37

• affects mostly middle age or older individuals. More common and less severe than type I and has more complex etiology
  
  • Results from reduced insulin secretion or insulin resistance or a combination of both
  • Typically preceded by obesity; obese patients with type II diabetes are invariably insulin resistant. Even non diabetic obese individuals have higher circulating insulin levels and proportionally decreased insulin responsiveness. Type II diabetes results when the increase in insulin exceeds the ability of the β cells to keep up with the demand. Deposition of islet amyloid may have a role in the “burnout” of β cells. In early stage type II diabetes, weight loss can reconstitute insulin responsiveness in the tissues

Question 38

Type 1b aka idiopathic diabetes

Answer 38

unusual form of phenotypic type I diabetes with almost complete insulin deficiency. Has strong hereditary component and no evidence of autoimmunity. Mainly in Africa and Asia

Question 39

Latent autoimmune diabetes of adulthood (LADA

Answer 39

form of type I diabetes with slow progressive, eventual insulin requirement in adulthood. Usually no ketoacidosis on presentation. Often misdiagnosed as type II; does not respond to oral medication to stimulate insulin secretion

Question 40

Gestational diabetes

Answer 40

developed in ~7% of pregnancies. Lactogen (human placental) has anti insulin activity that decrease insulin sensitivity and increase blood glucose. 90% become normoglycemic after delivery. Women with gestational diabetes are at increased risk for type II later in life

Question 41

Maturity onset diabetes of the young (MODY)

Answer 41

a spectrum of 6 diseases that are monogenic autosomal dominant diseases

Question 42

MODY type 2

Answer 42

Genetic defect: glucokinase gene
PNDM (complete absence of functional GK)

Frequency: 15 to 31%

Beta cell defect: Defective glucokinase molecule, increased plasma levels of glucose are necessary to elicit normal levels of insulin secretion

Clinical features: Mild, stable, fasting hyperglycemia, often diagnosed during routine screening. Not progressive.

Risk of micro
vascular disease: Generally no

Optimal treatment: Diet

Question 43

MODY type 3

Answer 43

Genetic defect: Hepatocyte nuclear factor-1-alpha

Frequency: 52 to 65%

Beta cell defect: Abnormal insulin secretion, low renal threshold for glucose

Clinical features: Low renal threshold for glucose, +glycosuria

Risk of micro
vascular disease: Yes

Optimal treatment: Sulfonyl
ureas

Question 44

Lesch-Nyhan syndrome

Answer 44

partial HPRT deficiency causes hyperuricemia, but complete deficiency causes Lesch-Nyhan syndrome which causes dystonia, choreoathetosis, spasticity, mental retardation, and self-mutilation behavior. Presence of uric acid in urine is early sign of disease and many patients die early from uric acid neuropathy. Neurological involvement is due to deficiency in purine nucleotides because the brain has low capacity for de novo purine synthesis, so relies on salvage enzyme

Question 45

Severe combined immunodeficiency (SCID)

Answer 45

deficeincy in adenosine deaminase (20q13.11). ADA (adenosine deaminase) catalyzes irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, inhibiting cellular cloning and expansion of lymphocytes in response to a challenge. Treated with bone marrow transplants and now experimentally with enzyme replacement therapy

Question 46

Gout

Answer 46

• All purines are catabolized to uric acid which has low solubility at lower pH’s (esp in collection ducts in kidneys where urine is concentrated). Uric acid stones do not show up on normal x-rays unlike calcium phosphate stones (“normal” kidney stones), but does show up on ultrasound and can be treated with oral sodium bicarbonate to raise urine pH.
• In blood, uric acid is deprotonated and occurs most often as sodium urate at higher sodium concentrations. Sodium urate concentrations are normally between 3-7 mg/dL, and Na urate precipitates at 7 mg/dL, so small rise causes precipitation
• Hyperuricemia is increased blood uric acid which causes the formation of sodium urate crystals in subcutaneous tissues known as tophi. These are asymptomatic, but in joints, crystals cause inflammatory response of gouty arthritis
• Secondary hyperuricemia is caused by an underlying disease; e.g. psoriasis, hemolytic anemia, pernicious anemia, malignancies. Etc
• Primary hyperuricemia is caused by overproduction of uric acid, impairment of excretion, or both
• 2 enzymes have been implicated in gout occurrence:
  
  • Overactive PRPP synthetase increases de novo purine synthesis
  • Reduced activity of salvage enzyme HPRT which causes accumulation of substrates
    
    • Free base levels of cellular bases are increased, increasing substrate for uric acid synthesis
    • Cellular PRPP levels are increased
  • G6Pase deficiency is also implicated because G6P buildup stimulates the PPP which increases R5P presence, leading to PRPP stimulation and overproduction of purines

Question 47

Kwashiorkor

Answer 47

problem with children in third world caused b deficiency of protein in diet. Suffer muscle wasting and decreased plasma concentration of proteins. Results in increased interstitial fluid which causes edema and distended abdomen

Question 48

Cystinurua

Answer 48

defect in transport of Cis and basic amino acids (lys, arg, and ornithine) across brush border causing insoluble cys accumulation which accumulates in kidneys causing kidney stones

Question 49

Hartnup disease

Answer 49

genetic disorder where neutral amino acid uptake across the intestine and renal epithelial cells is inhibited. Leads to deficiency in essential amino acids; esp deficiency in Try which prevents serotonin, and niacin production; leads to symptoms similar to pellagra

Question 50

Hashimoto thyroiditis

Answer 50

autoimmune disease that affects the thyroid and result in decreased thyroid hormone deficiency. Causes hypothyroidism; marked by fatigue, depression, constipation, abnormal cold sensitivity, and modest weight gain. Treated by thyroid hormone administration

Question 51

Graves disease

Answer 51

autoimmune disease where Abs bind to thyroid stimulating hormone (TSH) receptor and mimic TSH affects. Leads to goiter formation, fatigue, restlessness, increased bowel movements, increased respiration and heat tolerance, and weight loss. Treated by surgical resection of thyroid gland, radioactive iodine to decrease thyroid mass, or pharmacological intervention with antithyroid drugs like propylthiouracil an methimazole

Question 52

Phenylketonuria (PKU)

Answer 52

• Deficiency in enzymes phenylalanine hydroxyls (PAH) affects 1/10,000 births of white infants. Clinical PKU is defined as phe levels 5X normal
• Homozygotes develope hyperphenylalaninemia and PKU. Infants are normal at birth, but as Phe levels increase it causes brain impairment, metal retardation by 6 months if untreated. Also leads to light skin and hair due to decreased tyr (melanin precursor)
• Due to an inability to metabolize phe to tyr, leading to metal and developmental defects secondary to phe accumulation
• 98% due to change in gene sequence, 2% due to disfunction in synthesis/recycling of cofactor for PAH tetrahydrobiopterin
• Current treatments is protein free diet until age ~6. Mothers with PKU must be on the diet when pregnant or the baby has 90% chance of developmental disorders

Question 53

Galactosemia

Answer 53

• Autosomal recessive decency in galactose-1-phosphate uridyltransferase (GALT) affecting 1/60,000 births
• Inability to metabolize galactose results in gal1P and galactitol accumulation in liver, spell, kidney, eye, and cerebral cortex. Leads to cataracts, hepatomegaly and cirrhosis, and CNS damage
• Symptoms include vomiting and diarrhea days after milk ingestion, jaundice, hepatomegaly, and aminoacidurea. E. Coli speticemia incidence increases

Question 54

• Tay-Sachs disease

Answer 54

• Hexosimidnidase β deficiency manifesting as GM2 gangliosidosis; accumulation of GM2 gangliosides in lysosomes of the brain, heart, liver, and spleen. Common in Ashkenazi Jewish population 1/30 are carrier
• Major involvement is in the CNS, PNS, and retina. Possibly due to lack of misfolded protein response in cells with mutated hexosiminidase A proteins, so clinical trials of chaperones that can cross the blood brain barrier are underway.
• Most common variant of tay-sachs results in normal birth, with motor weakness between 3-6 months, followed by neurological impairment, blindness, and progressive neurologic dysfunctions leading to death between 2-3 years

Question 55

• Niemann-Pick disease types A and B

Answer 55

• Deficiency in acid sphingomyelinase leading to accumulation of sphingomyelin; also common in ashkenazi jews
• Type A has no sphingomyelinase activity and leads to dysfunction of organs with high phagocytic cell content like spleen, liver, bone marrow, and lungs. Leads to splenomegaly and CNS neuropathy. Results in severe organomegaly and neurologic deterioration that leads to death within 3 years
• Type B has residual activity, leading to organomegaly with no CNS involvement

Question 56

• Niemann-Pick disease type C

Answer 56

• Deficiency in lipid transport genes NPC1 and NPC2 leading to accumulation of cholesterol and gangliosides like GM1 and GM2. Bot genes are involved in cholesterol transport fro lysosomes to cytoplasm.
• Heterogenous, but mostly manifests in ataxia, dystonia, dysarthria, and psychomotor regression

Question 57

• Gaucher Disease

Answer 57

• Mutation in glucocerebrosidase resulting in accumulation of glucocerebroside in mononuclear phagocytes. Results in “gaucher cells”- enlarged macrophages that secrete IL-1 & 6 and TNF-α
• Type 1 variant: nonneuronopathic form accounts for 99% of cases
• Types 2 and 3 are neuronopathic; type 2 is earlier onset and more severe than type 3. Both results n convulsions and mental deterioration
• Patients with gaucher disease have 20x higher risk of Parkinson’s due to mutation in glucocerebrosidase
• Treatments include IV infusion with recombinant glucocerebrosidase and substrate reduction therapy where oral inhibitor of glucosylceremide synthase is administered to prevent accumulation of glucocerebrosides. Experimental therapy includes transplantation with genetically modified hematopoietic stem cell that has the missing gene

Question 58

• Mucopolysaccharidosis (MPS)

Answer 58

• Defective degradation of mucopolysaccharides resulting in accumulation of tissue dermatan sulfate heparin sulfate, keratin sulfate, and chondroitin sulfate
• Results in hepatosplenomegaly, skeletal deformities, heart valve lessons, lesions of the brain, and sub endothelial arterial deposits esp in coronary arteries. This leads to myocardial ischemia resulting in MI and cardiac decompensation resulting in death. All except for Hunter syndrome (X linked) are autosomal recessive

Question 59

MPS type I aka Hurler syndrome

Answer 59

results in cardiac complications and lysosomal inclusions in neurons leading to mental retardation

Question 60

MPS type II aka Hunter syndrome

Answer 60

has a different enzyme difficiency with the same product accumulation

Question 61

• Fabry Disease

Answer 61

• X linked deficiency lysosomal in α-galactosidase A leading to accumulation of globotriaosylceremide
  * Onset in early childhood; leads to widely varying symptoms including Acroparesthesia (burning, tingling, or pricking sensations or numbness in the extremities present on awaking and of unknown cause or produced by compression of nerves during sleep), current fevers, corneal and lenticular opacities, and anhydrous/hypohydrosis
  * Treated by pain management, valve replacement, dialysis or renal transplantation, and enzyme therapy