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Diseases Flashcards

1
Q

Adenosine Deaminase Deficiency

A

Is required for degradation of adenosine and deoxyadenosine

  • Decrease ADA
  • Increase dATP
  • Decrease Ribonucleotide reductase activity
  • Decrease DNA precursors in cells
  • Decrease Lymphocytes

** One of the major cause of autosomal recessive SCID.

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2
Q

Lesch-Nyhan syndrome

A

X-linked recessive

Defective purine salvage.

Absent “HGPRT”
H- Hyperuricemia
G- Gout
P- Pissed off (aggression, self-mutilation)
R - Red / Orange crystals in urine
T - Tense muscles (dystonia)

Treatment : Allopurinol, Febuxostat

  • Decrease GMP (from guanine)
  • Decrease IMP (from hypoxanthine) formation
  • Increase in purine synthesis (increase PRPP amidotransferase activity)
  • Excess Uric acid production

Findings: intellectual disability, self-mutation, aggression, hyperuricemia (red/orange “sand” [sodium urate crystals] in diaper), gout, dystonia, macrocytosis

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3
Q

Zellweger Syndrome

A

Inheritance: Autosomal Recessive

Mutation: Disorder of peroxisome biogenesis due to mutated PEX genes.

Clinical Presentation: Hypotonia, seizures, jaundice, craniofacial dysmorphia, hepatomegaly, early death.

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4
Q

Refsum Disease

A

Inheritance: Autosomal recessive

Mutation: Disorder of a-oxidation which leads to buildup of phytanic acid due to inability to degrade it.

Clinical Presentation: Scaly skin, ataxia, cataracts / night blindness, shortening of 4th toe, epiphyseal dysplasia.

Treatment: Diet, Plasmapheresis

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5
Q

Adrenoleukodystrophy

A

Inheritance: X-linked recessive

Mutation: Disorder of B-oxidation due to mutation in ABCD gene

Leads to: VLCFA buildup adrenal glands, white (Leuko) matter of brain, testes

Clinical Presentation: progressive disease that can lead to adrenal glad crisis, progressive loss of neurological function, death.

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6
Q

Primary Ciliary Dyskinesia

A

Inheritance: Autosomal Recessive

Mutation: Dynein arm defect

Leads to: immotile cilia, and/ or dysfunctional ciliated epithelia.

Clinical Presentation: Kartagener syndrome (PCI with situs Inversus).

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7
Q

What is Collagen?

A

Most abundant protein in the human body.
- Extensively modified by post translational modification.
- Organizes and strengthens extracellular matrix.
- Types I to IV are the most common types in humans.

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8
Q

Name Collagen Types I to IV.

A

Type I: Skeleton

Type II - Cartilage

Type III - Arteries

Type IV - Basement membrane

SCAB

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9
Q

Type I (Collagen)

A
  • Bone and Tendon
  • Decrease production in osteogenesis imperfecta type I.

Most common (90%) - Bone (made by osteoblasts)

Skin, Tendon, dentin, fascia, cornea, late wound repair.

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10
Q

Type II (Collagen)

A

Cartwolage

  • cartilage (including hyaline), vitreous body, nucleus pulposus
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11
Q

Type III (Collagen)

A

Deficient in vascular type of Ehlers-Danlos syndrome (threE D)

  • Reticulin - skin, blood vessels, uterus, fetal tissue, early wound repair
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12
Q

Type IV (Collagen)

A

Basement membrane / Basal lamina (glomerulus, cochlea), lens

Under the floor (Basement membrane)

  • Defective: in Alport Syndrome; targeted by autoantibodies in Goodpasture syndrome.
  • Myofibroblasts are responsible for secretion (proliferation stage) and wound contraction
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13
Q

De Vivo Disease

A

(GLUT Transporter Disease)

Mutation: GLUT1

Inheritance: AD

Clinical Presentation: Seizures, Microcephaly, Motor Dysfunction

Notes:
- Low Glucose in CSF / brain
- RX: Ketogenic Diets

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14
Q

Pyruvate Kinase Deficiency

A

(Glycolysis Disease)

Mutation:
- PKD

Inheritance:
- AR

Clinical Presentation:
- Echinocytes (hedgehog shape) in peripheral smear, Hemolytic anemia (Low RBC’s), Jaundice, increased unconjugated bilirubin*, splenomegaly; no Heinz bodies.

Notes:

  • Lack of pyruvate, decrease lactate and ATP in RBCs, inhibits NA+ / K +

-ATPase PUmp causes loss of K+ and water. Normal LDH

-Reduced affinity*

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15
Q

Pyruvate Dehydrogenase Complex ( PDHc Deficiency)

A

(Glycolysis Disease)

Mutation:
- PDH (e1 subunit)

Inheritance: XD

Clinical Presentation:
- Seizures, Intellectual disabilities, Microcephaly, epilepsy

Notes:
- Mitochondrial Matrix. Inability to convert Pyruvate to Acetyl CoA.

  • Rx: High does of vitamin B1 (TPP), ketogenic diet (High fat low carb diet)
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16
Q

Vitamin B1 (Thiamine Pyrophosphate) Deficiency

A

( Vitamin / Coenzyme Disease)

Mutation:
- PDH (oxidative decarboxylation) and transketolase

Function:
Edematous legs of a patient with wet beriberi.
a cofactor for several enzymes such as thiamine pyrophosphate (TPP)

  • pyruvate dehydrogenase (glycolysis)
  • α-ketoglutarate dehydrogenase (TCA cycle)
  • transketolase (HMP shunt)
  • branched-chain AA dehydrogenase (metabolism of Val, Leu, Ile)

Deficiency:
- causes alcoholism most common cause in US
- EtOH interferes with thiamine absorption in small intestine
- malnutrition
- non-enriched rice

symptoms:
impaired glucose breakdown due to decreased activity of pyruvate dehydrogenase
leads to ATP depletion
- highly aerobic tissues are affected first

Wernicke’s syndrome
- ataxia, confusion, nystagmus, ophthalmoplegia

Korsakoff’s syndrome
- confabulation, psychosis, and mammillary body hemorrhage
- beriberi

dry beriberi
- peripheral neuropathy due to demyelination
- symmetrical muscle wasting
- no fluid retention

wet beriberi
- high-output cardiac failure (dilated cardiomyopathy)
- edema

diagnosis:
- can be made by measuring increased transketolase activity after thiamine administration
- mechanism
- thiamine is a cofactor necessary for the function of transketolase
- diagnosis of thiamine deficiency is made by history

management:
- patients that present with thiamine deficienty should be treated with thiamine first
- after thiamine has been administered, can then administer glucose in IV fluids

mechanism:
- thiamine is a cofactor for enzymatic steps in glycolysis
- administering glucose before thiamine could further decrease thiamine levels for enzymes like transketolase which could exacerbate Wernicke-Korsakoff syndrome

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17
Q

Wet Beri Beri

A

( Vitamin / Coenzyme Disease)

Mutation:
- Lack B1 (Thiamine)

Inheritance:

Clinical Presentation:
- Congestive Cardiac Failure, Lactic Acidosis, peripheral Edema, Arrhythmias

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18
Q

Wernike’s Encephalopathy

A

(Vitamin / Coenzyme Disease)

“ Wet Brain Syndrome”

Mutation:
- Lack B1 (Thiamine)

Inheritance:

Clinical Presentation:
- Ataxia, Opthalmoplegia, Confusion

Notes:
- Dry Beri Beri

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19
Q

Vitamin B2 Deficiency (Riboflavin)

A

(Vitamin / Coenzyme Disease)

Mutation:
- Lack B2 (Riboflavin)

Function
cofactor for
- oxidation and reduction (e.g., FADH2)
- succinate dehydrogenase
precursor to FAD and FMN
involved with many dehydrogenase enzymes

Deficiency
- causes severe malnourishment

symptoms
- cheilosis (inflammation of the lips and scaling and fissures at the corners of the mouth)
- corneal vascularization
- dry skin
- magenta-colored tongue

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20
Q

Vitamin B3 Deficiency (Niacin)

A

( Vitamin / Coenzyme Disease)

Mutation:
- Lack B3 (Niacine)

Function
- constituent of NAD+and NADP+ (used in redox reactions)
- derived from tryptophan
- involved with many dehydrogenase enzymes
- synthesis requires vitamin B2 and B6

Deficiency
- causes
- diets low in tryptophan or niacin
- corn staple diets

Hartnup disease
↓ tryptophan absorption in kidneys and small intestine

malignant carcinoid syndrome
↑ tryptophan metabolism in production of serotonin

INH therapy
↓ vitamin B6 leading to ↓ niacin synthesis

symptoms
- glossitis
- severe deficiency leads to pellagra (3 D’s)
- diarrhea, dermatitis, dementia

Excess
- causes
- nicotinic acid given at high doses as hyperlipidemic treatment (raised HDL)

symptoms
- facial flushing
- mediated by prostaglandins, treated with aspirin
- intrahepatic cholestasis
- hyperglycemia
- hyperuricemia

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21
Q

Chronic Granulomatus

A

( Free Radicals Disease)

Mutation:
- NADPH oxidase complex

Inheritance: XR

Clinical Presentation:
- Chronic recurrent infectious, abscess formation, Osteomyelitis, Pneumonia, Bacteremia / Fungemia

Notes:
- Phagocytes cannot destroy microbes, lack of H2O2

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22
Q

NADPH Oxidase Deficiency

A

( Free Radicals Disease)

Mutation:
- Lack of Superoxide

Inheritance:
- X-linked or AR

Clinical Presentation:
- Increased catalase + recurrent pyogenic infections

NoteS:
- Negative NBT test / abnormal dihydrorhodamine test

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23
Q

Glucose - 6 - Phosphate- Dehydrogenase Deficiency (G6PD) Deficiency

A

( Pentose Phosphate Pathway Disease)

Mutation:
- G6P Dehydrogenase

Inheritance:
- XR

Clinical Presentation:
- Pt okay until increase oxidative stress, Hemolytic anemia, Bite cells, degmacytes in peripheral smear: hemoglobinuria after a free radical insult

Notes:
- Decreased NADPH in RBCs; Inhibition of Glutathione dehydrogenase.
- Increased lactate dehydrogenase.
- Decreased haptoglobin.

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24
Q

Von Gierke

A

( Glycogen Metabolism Disease)

Mutation :
- Glucose - 6- Phosphotase

Inheritance:
- Hypoglycemia, Growth failure, Hepatomegaly, ketosis, lactic acidosis, renomegaly (Enlargement of Kidney).

Notes:
- Low glucose,
- Low phosphate,
- High pyruvate,
- High glucose-6-phosphate,
- High acetyl-CoA,
- High lactate,
- High uric acid,
- High beta oxidation and fatty acids,
- and high ketone bodies.

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25
Q

Anderson’s Disease

A

( Glycogen Metabolism Disease)

Mutation:
- Branching Enzyme / Glucantransferase

Inheritance:

Clinical Presentation:
- Cardiac or liver failure, very long amylopectin chains casing liver to become cirrhotic.

Notes:
- Abnormal, many long chains with few branches

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26
Q

Cori Disease

A

( Glycogen Metabolism Disease)

Mutation:
- Debranching Enzyme / a-1,6 Glucosidase

Inheritance:

Clinical Presentation:
- Mild Hypoglycemia, hepatomegaly that diminishes with age

Notes:
- Many short branches ( limit dextrins), Abnormal Glycogen

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27
Q

McArdles Disease

A

(Glycogen Metabolism Disease)

Mutation:
- Muscle Glycogen Phosphorylase (Myoposphorylase)

Inheritance:

Clinical Presentation:
- Muscle cramps, absent normal anaerobic production of lactate during exercise

Notes:
- No muscle glycogen breakdown

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28
Q

Her Disease

A

( Glycogen Metabolism Disease)

Mutation:
- Liver Glygcogen Phosphorylase

Inheritance:

Clinical Presentation:
- Hypoglycemia, Hepatomegaly

Notes:
- No liver glycogen breakdown

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29
Q

Pyruvate Carboxylase Deficiency

A

(Gluconeogenesis Disease)

Mutation:
- Pyruvate Carboxylase

Inheritance: AR

Clinical Presentation:
- Hypoglycemia + Hyperketosis, Metabolic Acidosis, Failure to Thrive, developmental delay, hyperammonemia (due to the malfunctioning of urea cycle).

Notes:
- Decreased oxaloacetate
- Decreased glutamate - decreased neurotransmitter synthesis
- Malfunction of citric acid cycle - decreased ATP
- Malfunction of gluconeogenesis - decreases glucose
- Accumulation of acetyl CoA in the liver

Treatment: Biotine Supplementation, aspartate supplementation

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30
Q

Fructosuria

A

( Fructose Metabolism Disease)

Mutation:
- Fructokinase

Inheritance: AR

Clinical Presentation:
- Fructose in urine, UTI, dehydration

Notes:
- No fructose to F1P

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31
Q

Hereditary Fructose

A

( Fructose Metabolism Disease)

Mutation:
- Aldolase B

Inheritance:

Clinical Presentation:
- Hypoglycemia, nausea, hepatomegaly, metabolic acidosis. Weaning

Notes:
- Phosphate trapping.
- High fructose diets, fruits.
- Accumulation of fructose 1 P04
- Inhibition of glycogenolysis and gluconeogenesis

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32
Q

Nonclassical Galactosemia

A

(Fructose Metabolism Disease)

Mutation:
- Galactokinase

Inheritance: AR

Clinical Presentation:
- Cataracts, high blood and urine galactose

Notes:
- Accumulation of galactose

33
Q

Classical Galactosemia

A

(Fructose Metabolism Disease)

Mutation:
- GALT (Galactose-1-phosphate Uridyltransferase)

Inheritance:

Clinical Presentation:
- Mental retardation, Hypoglycemia, cataracts, liver damage - hemorrhage Jaundice, Cirrhosis, vomiting. (Breast Feeding)

Notes:
- Accumulation of galactose 1 PO4 - osmotic damage and phosphate trapping.
- Inhibition of glycogenolysis.
- Cataracts due to Galactitol accumulation.

34
Q

Arsenite

A

( Glycolysis Disease)

Mutation:
- a-Ketoglutarate Dehydrogenase and Pyruvate Dehydrogenase (PDH)

Inheritance:

Clinical Presentation:
- no TCA

Notes:
- Inhibits pyruvate to Acetyl CoA.
- Inhibits alpha- KDH by binding to SH groups of lipase.

35
Q

Arsenate

A

(Glycolysis Disease)

Mutation:
- Glyceraldehyde-3-Phospate Dehydrogenase (G3PD)

Inheritance:

Clinical Presentation:
- No second half of Glycolysis

Notes:
-Defects on G3P to 1, 3BPG

36
Q

Franconi Bickel syndrome / Glycogen Storage Disease Type XI

A

(GLUT Transporter Disease)

Mutation:
- GLUT2

Inheritance: AR

Clinical Presentation:
- Failure to thrive, Hepatomegaly (secondary to Glycogen Accumulation), Renal Dysfunction, Vitamin D resistant rickets.

Notes:
- Impaired transport of glucose, galactose, fructose.
- Fasting ketotic hypoglycemia and postprandial hyperglycemia.

37
Q

Pompe’s Disease

A

(Glycogen Metabolism Disease)

Mutation:
- Acid Maltase / lysosomal a-1,4-Glucosidase

Inheritance:
- Hypotonia, Cardiomegaly, death by age 2 years

Notes:
- Accumulation of lysosomal glycogen deposits.

38
Q

Xeroderma Pigmentosum

A

caused by damage to XP proteins that function in nucleotide excision repair.

39
Q

Ataxia Telangiectasia

A

caused by damage in ATM protein (cell checkpoint protein that allows entry in homologous repair pathway).

40
Q

Breast/Ovarian/Prostate cancer

A

increased risk caused by damage to BRCA1/2 proteins (function in homologous repair pathway)

41
Q

Nijmegen Breakage Syndrome

A

caused by defect in NBM proteins that function in repair of dsDNA.

42
Q

Bloom Syndrome

A

caused by defect in BLM protein that regulates chromosomes; excessive sister chromatid exchange.

43
Q

Werner Syndrome

A

caused by defect in WRN protein that regulates chromosomes and telomeres; defective base excision and homologous repair pathways.

44
Q

Fanconi Anemia

A

caused by defect in FA proteins; leads to defective interstrand crosslink repair in chromosomes.

45
Q

HPNCC/Lynch Syndrome

A

loss of function in mismatch repair (MSH and MLH) proteins.

46
Q

Huntington’s, Fragile X, Friedriech Ataxia, Myotonic Dystrophy

A

STR expansions (trinucleotide repeats) caused by slippage.

47
Q

Emery-Dreifuss Muscular Dystrophy

A

disease caused by mutation in either emerin or LA/C; characterized by contractures in neck, elbows, ankles, that cause deformation and limited motion, arrhythmias, hypotonia, atrophy, sudden heart failure, and fragile nuclei.

48
Q

Dilated Cardiomyopathy

A

caused by LA/C defect that cause fragile nuclear lamina, congestive heart failure, and cell death.

49
Q

Lipodystrophy

A

caused by defects in LA/C mutation that causes accumulation of adipose in face and neck and absence in rest of body.

50
Q

Hutchinson-Gilford Progeria Syndrome

A

autosomal dominant disease with onset at birth/early infancy caused by alterations in LA.; premature aging, prominent eyes, no subcutaneous fat, joint stiffness, alopecia, arteriosclerosis.

51
Q

Spinal Muscular Dystrophy

A

autosomal recessive disease caused by mutation in SMNs that causes defects in snRNPS, faulty pre-mRNA splicing, loss of motor neurons in spinal cord and brainstem.

52
Q

Cystic fibrosis

A

autosomal recessive disease caused by misfolding of the CFTR protein (plasma transmembrane protein in epithelial cells that functions in channeling Cl- ions); characterized by frequent infections, malabsorption in the GI tract, bronchiectasis (permanently dilated bronchi), chronic cough and dyspnea, and lung obstructions.

53
Q

Class I hypercholesterolemia

A

autosomal dominant disease caused by defects in synthesis of LDL receptor protein; inability to clear LDL and continous cholesterol synthesis.

54
Q

Class II hypercholesterolemia

A

autosomal dominant disease caused by defects in transportation of LDL protein from RER; Class II hypercholesterolemia to clear LDL and continous cholesterol synthesis.

55
Q

Class IV hypercholesterolemia

A

LDL receptors are made but cannot cluster on cell surface to form a coated pit correctly due to poor interaction with adaptin; least severe form.

56
Q

I-cell disease

A

caused by deficiency in N-acetylglucosamine phosphotransferase that results in a failure to produce M6P protein tags and formation of lipofuscin bodies.
characterized by restricted join movement, skeletal abnormalities, psychomotor retardation, enlarged heart/liver/spleen.

57
Q

Botulism

A

flaccid paralysis disease caused by neurotoxins that cleave synaptobrevin (v-SNARE for motor neurons), preventing vesicle docking and fusion of acetylcholine.

58
Q

Tetanus

A

spastic paralysis disease caused by neurotoxins that is endocytosed into a neuron to enter nerves in the spinal cord that inhibit motor neurons; cleaves synaptobrevin to prevent release of GABA and glycine.
acetylcholine is continually released.

59
Q

Blistering disease/Epidermolysis Bullosa Simplex

A

autosomal dominant disease caused by ruptures in the basal layer of epithelium.
Caused by mutations in keratin 5/14.
Characterized by fragile skin, especially in palms/hands; minor mechanical stress/friction leads to blister formation.

60
Q

Epidermolytic Hyperkeratosis

A

autosomal dominant disease caused by mutation in keratin 1/10 of the middle layers of epidermis (stratum spinosum).
Characterized by easy blistering, formation of calluses and hard, scaly skin, chronic wounding, thickened skin.

61
Q

Epidermolytic Plantopalmar Keratoderma

A

disease caused by mutations in keratin 9.
Keratinocytes (keratin filled bodies) form on soles of feet and palms.
Caused by all forms of mendelian inheritance, environmental stress, etc.

62
Q

Dystrophic Epidermolysis Bullosa

A

autosomal dominant or recessive diseases caused by mutation in type VII collagen causing absence of anchoring fibrils.
Characterized by syndactyly (digit fusion), skin falling off, and scarring.

63
Q

Kwashiorkor

A

Causes
protein-deficient diet

Clinical Presentation:
skin lesions
pitting edema

↓ albumin leads to ↓ oncotic pressure in vasculature and loss of fluid into extravascular space
- ascites
- liver malfunction
- ↓ apolipoprotein synthesis
- fatty liver

defects in cell-mediated immunity
- ↓ in complement protein synthesis
muscle protein relatively unchanged

64
Q

Marasmus

A

Causes
protein- and caloric-deficient diet

Presentation
tissue and muscle wasting
- “broomstick” extremities
- breakdown of muscle protein for energy

loss of subcutaneous fat
variable edema

65
Q

Vitamin B5 (Pantothenate)

A

Function:

component of coenzyme A required for many enzymatic processes
- fatty acid synthase (fatty acid metabolism)
- acyl transferases
- pyruvate dehydrogenase (PDH)
- α-ketoglutarate dehydrogenase (TCA cycle)

Deficiency:
rare

symptoms:
dermatitis, enteritis, alopecia, and adrenal insufficiency

66
Q

Vitamin B6 (Pyridoxine)

A

Function:
converted to pyridoxal phosphate, a cofactor
used in
- transamination (e.g., ALT and AST in protein catabolism)
- decarboxylation reactions
- glycogen phosphorylase
- cystathionine synthesis
- heme synthesis
- required for the synthesis of niacin from tryptophan

Deficiency:
causes
- INH (isoniazid)
- oral contraceptives
- goat milk
- chronic alcoholism

symptoms:
convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias, cheilosis or stomatitis

67
Q

Vitamin B12 (Cobalamin)

A

Function:
- cofactor for homocysteine methyltransferase
- transfers CH3 groups as methylcobalamin
- cofactor for homocysteine + N-methyl THF → methionine + THF

  • cofactor for methylmalonyl-CoA mutase
    • metabolism of propionate (odd-chain fatty acid degradation) at the conversion of methylmalonyl CoA → succinyl CoA
    • folate not directly involved in this pathway
    • megaloblastic anemia with an elevated methylmalonyl CoA indicates B12 deficiency as opposed to folate
    • metabolism of Val, Met, ILe, Thr

Source:
- found only in animal products
- several years of reserves stored primarily in the liver

Deficiency:
causes
- pernicious anemia
- intrinsic factor required for absorption in the terminal ileum
- B12 not absorbed when intrinsic factor not produced from the parietal cells of the stomach

  • gastric bypass surgery
    • less intrinsic factor produced
  • resection of terminal ileum
    e.g., Crohn’s disease
  • malabsorption
    • sprue, enteritis

-bacterial overgrowth of terminal ileum
- diphyllobothrium latum (parasite)
- competes for B12 absoroption
- vegan diets
- use Schilling test to detect etiology of the deficiency
- differential process of radiolabeled B12
1. oral B12 + IM B12
2. B12 + intrinsic factor
3. B12 + antibiotics
4. B12 + pancreatic enzymes

symptoms:

  • macrocytic, megaloblastic anemia
    • found also in folate deficiencies
  • hypersegmented PMNs
  • neurologic symptoms due to abnormal myelin
    • paresthesias and subacute combined degeneration
      - dorsal columns of spinal cord degenerate causing loss of proprioception and vibration sensation
  • not found in folate deficiencies
  • could be reversible with administration of B12
    - severe symptoms and longer term B12 deficiency = more residual neurologic damage and less function regained
68
Q

Folic Acid

A

Functions:
- converted to tetrahydrofolate (THF), a coenzyme for 1-carbon transfer/methylation reactions
- important for the synthesis of nitrogenous bases in DNA and RNA (thymidylate synthase)
- recall: uridine + methyl group = thymidine

Deficiency:
most common vitamin deficiency in the United States
absorbed in the jejunum via the action of intestinal conjugate

causes
- dietary deficiency
- elderly
- goat milk
- seen in alcoholism and pregnancy
- liver stores last three months
- deficiency can be caused by several drugs
- e.g. phenytoin, sulfonamides, methotrexate, EtOH

findings:

  • macrocytic, megaloblastic anemia
  • hypersegmented neutrophils
  • homocysteinemia
    • ↑ risk of DVT and atherosclerosis
  • no neurologic symptoms + normal methylmalonic acid level (as opposed to vitamin B12 deficiency)
  • deficiency in pregnancy causes fetal neural tube defects
    • supplemental folic acid in early pregnancy reduces risk
69
Q

Biotin

A

Function:
cofactor for carboxylation enzymes (adds a 1-carbon group)
pyruvate carboxylase
- pyruvate (3C) → oxaloacetate (4C)
- gluconeogenesis
- acetyl-CoA carboxylase
- acetyl-CoA (2C) → malonyl-CoA (3C)
- fatty acid synthesis
- propionyl-CoA carboxylase
- propionyl-CoA (3C) → methylmalonyl-CoA (4C)
- odd-carbon fatty acids, Val, Met, Ile, Thr catabolism

Deficiency:
- relatively rare
- causes
- antibiotic use
- excessive ingestion of raw eggs
- contains avidin which binds biotin

symptoms:
dermatitis, alopecia, enteritis, lactic acidosis

70
Q

Vitamin C (Ascorbic Acid)

A

Function:
- antioxidant
- regenerates vitamin E
- ↓ oxidation of LDL
- keeps iron in Fe2+ reduced state
- ↑ intestinal absorption
- collagen synthesis
- essential for hydroxylation of proline and lysine
- prolyl and lysyl hydroxylases
- addition of hydroxyl group allows for hydrogen bonding between fibers
- without cross-linking triple helix shape cannot form
- synthesis of norepinephrine
- necessary for dopamine β-hydroxylase
- converts dopamine to NE
- hepatic synthesis of bile acids
- keeps THF in reduced form
- protects against nitrosylation of amides
- occurs in the stomach with presence of food preservatives
- nitrosamines/amides are carcinogenic

Source:
- found in fruits and vegetables
- British sailors carried limes to prevent scurvy

Deficiency:
- causes
- diet lacking citrus fruits and green vegetables
- infants on formula that is boiled too long
- excessive heat destroys vitamin C
- cigarette smoking

symptoms:
- scurvy
- swollen gums, bruising, perifollicular hemorrhage, poor wound healing, glossitis, ↑ bleeding time
- anemia due to combined iron and folate deficiency
- infantile scurvy
- 2-10 months
- excessively boiling formula

Excess:
symptoms
- formation of renal calculi made from calcium oxalate (vitamin excreted as oxalate)
- diarrhea, nausea, vomiting
- excess iron absorption in those predisposed (hemochromatosis, repeat blood transfusions)

71
Q

S-Adenosylmethionine (SAM)

A

Not a vitamin but an important cofactor

Synthesis:
- ATP + methionine → SAM
- regeneration of methionine (and thus SAM) is dependent on vitamin B12 and folate

Function:
- SAM transfers methyl units
- similar to THF
- SAM is required for the conversion of NE to epinephrine

72
Q

Lysosomal Storage Disease (by Deficient Enzymes)

                                                                  Sphingomyelinase
A

Sphingolipidoses

  • deficient in Niemann-Pick disease
    • sphingomyelin accumulates
      • histiocytes look “foamy”

Clinical presentation:

hepatosplenomegaly
anemia
cherry red spots on macula
death < 3 years
failure to thrive
neurodegeneration

inheritance:
AR
risk ↑ in Ashkenazi Jews

73
Q

Lysosomal Storage Disease (by Deficient Enzymes)

                                                                        α-galactosidase A
A

Sphingolipidoses

  • deficient in Fabry disease
    • ceramide trihexose accumulates

Clinical presentation:

peripheral neuropathy
- especially in hands and feet

angiokeratomas
- small purple blemishes on skin

impaired sweating, either hypo- or anhidrosis
cardiovascular disease
renal disease

inheritance:
XR

74
Q

Lysosomal Storage Disease (by Deficient Enzymes)

                                                                   β-galactocerebrosidase
A

Sphingolipidoses

deficient in Krabbe disease
galactocerebroside accumulates

Clinical presentation:

hyperactive reflexes
optic atrophy
developmental delay
presence of globoid cells
large multinucleated cells that contain PAS positive inclusions

inheritance:
AR

75
Q

Lysosomal Storage Disease (by Deficient Enzymes)

                                                                       β-glucocerebrosidase
                                                                              2nd Disease
A

Sphingolipidoses

deficient in Gaucher disease
glucocerebroside accumulates in cells of phagocytic cells

histiocytes (dendritic cells) look like wrinkled tissue paper
called Gaucher’s cells

Clinical presentation:

three types
- type I
- most common
- hepatosplenomegaly
- aseptic necrosis of heads of long bones
- mild anemia
- possible to live a normal lifespan

  • type II
    “infantile Gaucher”
    CNS involved
    death < 1 year
  • type III
    “juvenile Gaucher”
    severity < type II

inheritance:
AR
risk ↑ in Ashkenazi Jews

76
Q

Lysosomal Storage Disease (by Deficient Enzymes)

                                                                                 Arylsulfatase A
A

Sphingolipidoses

deficient in metachromatic leukodystrophy
cerebroside sulfate accumulates

Clinical presentation:
demyelination in CNS and PNS
resulting in ataxia and dementia

inheritance:
AR

77
Q

Lysosomal Storage Disease (by Deficient Enzymes)

                                                                     α-L-iduronidase
A

Mucopolysaccharides

deficient in Hurler syndrome
heparan sulfate and dermatan sulfate accumulates in heart and liver

Clinical presentation:
gargoyle-like facies
corneal clouding
progressive mental retardation

inheritance:
AR

78
Q

Lysosomal Storage Disease (by Deficient Enzymes)

                                                                          Iduronate sulfatase
A

Mucopolysaccharides

deficient in Hunter syndrome
heparan sulfate and dermatan sulfate accumulates

Clinical presentation:

severity < than Hurler’s
aggressive behavior
remember: hunter’s are aggressive
corneal clouding absent

inheritance:
XR

MTM (9 decks)

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