Diseases pt 1

Question 1

Pellagra (448)

Answer 1

Deficiency of B3 (niacin). Causes clinical triad of 3D’s (dementia, diarrhea, dermatitis) and could cause death.
Note that excess B3 causes itching, flushing and vasodilatation.

Question 2

Lactose intolerance (473)

Answer 2

• Primary intolerance: hereditary deficiency of lactase (common in africa and asian)
• Secondary intolerance: occur in any age
• Lactose increases the osmotic load, giving rise to diarrhea & flatulence

Question 3

what is Pyruvate kinase relation to Hemolytic anemia?

Answer 3

Its deficiency leads to hemolytic anemia. Since RBCs have no mitochondria, it depends totally on glycolysis to provide ATP. With no energy, it is hard to maintain the biconcave shape and function of the Na/K ion pump leading to swelling and early lysis.

Question 4

What is the relation between PDH deficiency and lactic acidosis?

Answer 4

Deficiency of PDH leads to pyruvate build up, and pushes its conversion to lactate (lactic acidosis). Causes neurologic deficits, persistent acidosis and hypotonia. Treatment is sometimes with high fat diet, thereby bypassing the PDH reaction

Question 5

What is chronic granulomatous disease?

Answer 5

The deficiency of NADPH oxidase complex leading to neutrophils that don’t produce superoxide. So neutrophils engulf, but can not kill the bacteria

Question 6

Hereditary fructose intolerance (HFI)

Answer 6

Deficiency of aldolase B that cleaves fructose-1-phosphate into DHAP and glyceraldehyde. Leads to accumulation of fructose-1-phosphate in the liver, which inhibits glycogenolysis (glycogen phosphorylase) and gluconeogenesis, resulting in severe hypoglycemia. Treatment is removal of fructose and sucrose from diet
see p.498

Question 7

Galactosemia

Answer 7

Autosomal recessive disease. Caused by deficiency of galactokinase (mild galactosemia) or galactose-1-phosphate uridyl transferase (severe)
Accumulated galactose is converted to galactitol in CNS (retardation) and lens of the eye (cataracts).
Galactose-1-phosphate accumulation leads to hepatomegaly. Treatment is exclusion of galactose and lactose from diet.

Question 8

Hypercholesterolemia or type II hyperlipoproteinemia are caused by…..

Answer 8

defective LDL receptors. Characterized by elevated LDL cholesterol. This has a correlation to coronary atherosclerosis

Question 9

Hartnup disease (p. 344)

Answer 9

Autosomal recessive. Defect in neutral amino acids (especially tryptophan) transport in the intestine & kidney
* Diagnosed by aminoaciduria

Question 10

Cystinuria (p. 344)

Answer 10

Autosomal recessive. Defect in the transport of lysine, cystine, arginine and ornithine resulting in their excretion in urine
* Low solubility of cystine leads to kidney stones

Question 11

Maple Syrup urine disease (p. 349)

Answer 11

autosomal recessive. Deficiency of BCKA-DH. The urine has a maple syrup odor. Causes brain damage and death
* The levels of branched chain amino acids (leucine, isoleucine, valine) and their correspondent alpha keto acids are elevated in plasma and urine

Question 12

Hirschsprung disease (p. 404)

Answer 12

congenital defect of GIT plexi, leading to severe obstruction, megacolon & constipation

Question 13

Von Gierke’s’ disease (p. 486)

Answer 13

decrease glucose and high serum lactate & pyruvate, due to low level glucose-6-phosphatase
* There is enlargement of liver and kidneys due to glycogen accumulation

Question 14

Osteitis fibrosa cystica (p. 505)

Answer 14

Increase PTH leading to increase bone metabolism and causes the kidney to waste calcium. May cause kidney stones

• There is increased bone resorption and fibrous replacement of marrow causing cystic spaces (brown tumors)
• Also called Recklinghausen disease of bone

Question 15

Renal osteodystrophy is …..

Answer 15

decrease in synthesis of calcitriol causing bone mineralization defect

Question 16

Presbycusis is …….

Answer 16

the gradual hearing loss in elderly

Question 17

Dysgeusia is …… while ageusia is …..

Answer 17

disturbance of taste

complete loss of taste sensation

Question 18

Define:

1. Anosmia
2. Dysosmia
3. Hyposmia

Answer 18

1. complete loss of smell (e.g in cold, Kallman syndrome)
2. Disturbance of smell
3. reduced smell

Question 19

Kallmann syndrome is …..

Answer 19

Hypogonadism (due to low GnRH) and anosmia (loss of smell)

Question 20

Waterhouse–Friderichsen syndrome is …..

Answer 20

defined as adrenal gland failure due to bleeding into the adrenal glands, caused by severe bacterial infection (most commonly the meningococcus Neisseria meningitidis)
* causes DIC, low BP, shock

Question 21

What is the difference between Cushing’s syndrome and disease?
(see p. 429 for complete symptoms, FA)

Answer 21

• The disease is caused by pituitary tumor secreting ACTH. Causing hyperpigmentation, in addition to high cortisol levels
• The syndrome is caused by cortisone intake, ↑ cortisol (from adrenal tumor), or ectopic ACTH producing tumor (oat cell, basal cell etc…)

Question 22

Plummer disease is …..

p. 434 FA

Answer 22

toxic multinodular goiter. incidence increases with age.

• Multiple secreting thyroid adenomas within the gland
• No exophthalamus like Grave’s disease
• Never seen in children
• More in females over 60

Question 23

Marfan syndrome (p. 145)

Answer 23

Autosomal dominant, connective tissue disorder.

• Characteristics: arachnodactyly, ligamentous laxity, subluxed lens, tall stature, dissecting aortic aneurysm, mitral prolapse
• Short life span due to rupture of aorta

Question 24

Familial polyposis coli (p. 145)

Answer 24

• Autosomal dominant
• adenomatous polyps throughout the colon
• Treatment is surgical removal of the entire colon in the third decade of life, due to carcinoma of the colon
• Gardener’s syndrome has colonic polyps with soft & hard tissue tumors. The risk of cancer is 100%

Question 25

Adult polycystic kidney disease (p.145)

Answer 25

• Autosomal dominant
• renal cysts, increase with age
• characteristics are large kidneys, hypertension, anemia, renal failure

Question 26

Huntington disease (p.145)

Answer 26

• Autosomal dominant
• Characteristic: involuntary chorea, change in behavior, cognitive impairment. Death follows after about 20 years
• Associated with degeneration of the caudate nucleus (in the basal ganglia)
• The gene is localized to the short arm of chromosome 4

Question 27

Wilm Tumor (p. 145)

Answer 27

• Autosomal dominant
• Tumor involving the kidneys of children under 5 years of age. It may reach enormous size
• Characterized by immature tubules with primitive mesenchyme (contain bone, epithelium, muscle), hypertension, hematuria
• Tumor gene is localized to chromosome 11p
• Metastasizes to liver, lung, adrenals, lymph
• 90% survival rate after surgery

Question 28

Von Gierke disease or type I glycogen storage disease (p. 145)

Answer 28

• Autosomal recessive
• deficiency of glucose-6-phosphatase
• There is hepatomegaly and renomegaly

Question 29

Pompe disease or type II glycogen storage disease (p. 145)

Answer 29

• Autosomal recessive
• deficiency of alpha 1,4 glucosidase (same function as glycogen phosphorylase)
• Characteristic: glycogen accumulation in the muscle lysosomes
• There is hepatomegaly and cardiomegaly

Question 30

Type III & IV glycogen storage disease (p.146)

Answer 30

• Autosomal recessive
• Type III: deficiency of debranching enzyme
• Type IV: deficiency of branching enzyme

Question 31

McArdle disease or type V glycogen storage disease (p. 146)

Answer 31

• Autosomal recessive
• specific for skeletal muscles
• Defect in glycogen phosphorylase
• There is muscle cramping and myoglobinuria

Question 32

Type VI glycogen storage disease (p.146)

Answer 32

• Autosomal recessive

* Defect in liver glycogen phosphorylase

Question 33

List the type of lysosomal storage disease or mucopolysaccaridoses (p.146)

Answer 33

• all Autosomal recessive except MPS II
  1. MPS I H (Hurler)
  2. MPS I S (Scheie)
  3. MPS I H/S
  4. MPS II (Hunter)
  5. MPS III (Sanfilippo)
  6. MPS IV (Morquio)

Question 34

Tay-Sachs disease (p. 146)

Answer 34

• Autosomal recessive
• Also called gangliosidosis type I
• Deficiency of hexosaminidase A, leads to accumulation of G m2 ganglioside.
• Affects all organs, but more in brain, retina, peripheral nervous system
• Onset at 6 months of age with exaggerated startle reflex. Progressive mental, motor & visual deterioration, with cherry red spot on macula
• Highest incidence in Ashkenazic Jews

Question 35

Gaucher disease (p. 146)

Answer 35

• Autosomal recessive
• Defect in beta-glucocerebrosidase, leading to accumulation of glucocerebroside in brain, liver, spleen, bone marrow
• Characteristic: mental retardation, neurologic deficit, hepatosplenomegaly

Question 36

Niemann-Pick disease (p. 146)

Answer 36

• Autosomal recessive
• Deficiency of sphingomyelinase, leading to accumulation of sphingomyeline & cholesterol in reticuloendothelial tissues
• Characteristics: hepatosplenomegaly, foam cells in bone marrow, mental deficit, death by age 3

Question 37

Farber disease (p. 340)

Answer 37

Deficiency of ceramidase, leads to ceramide accumulation

* characteristic: hoarseness, dermatitis, hepatomegaly, mental retardation skeletal deformity

Question 38

Fabry disease (p. 340)

Answer 38

• X-linked recessive
• deficiency of alpha-galactosidase
• characteristic: renal failure, telangiectasias, skin rash, pain in lower extremities

Question 39

Cystic Fibrosis (p. 146)

Answer 39

• Autosomal recessive
• Abnormality in Cl channels, which leads to very thick mucus
• Diagnosed by increased Na & Cl levels in sweat, and low H2O and bicarbonate secretion from the pancreas, leading to viscous secretion
• Patients suffer steatorrhea (pancreatic insufficiency, resulting in low vit A, D, E, K), pulmonary obstruction (due to thick secretion, leads pseudomonas infection)
• Meconium ileus in newborns

Question 40

Alpha-1-antitrypsin deficiency is ……

Answer 40

• Autosomal recessive
• When A1AT is deficient, neutrophil elastase is free to break down elastin, which contributes to the elasticity of the lungs
• Causes emphysema of lower lung, in contrast to smoking, where it affects the upper lobes more

Question 41

Krabbe’s disease

Answer 41

• Autosomal recessive. A lipid storage disease

* Galactocerebrosidase deficiency, leads to accumulation of galactocerebrosides