Diseases Flashcards
Adenosine Deaminase Deficiency
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.
Lesch-Nyhan syndrome
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
Zellweger Syndrome
Inheritance: Autosomal Recessive
Mutation: Disorder of peroxisome biogenesis due to mutated PEX genes.
Clinical Presentation: Hypotonia, seizures, jaundice, craniofacial dysmorphia, hepatomegaly, early death.
Refsum Disease
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
Adrenoleukodystrophy
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.
Primary Ciliary Dyskinesia
Inheritance: Autosomal Recessive
Mutation: Dynein arm defect
Leads to: immotile cilia, and/ or dysfunctional ciliated epithelia.
Clinical Presentation: Kartagener syndrome (PCI with situs Inversus).
What is Collagen?
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.
Name Collagen Types I to IV.
Type I: Skeleton
Type II - Cartilage
Type III - Arteries
Type IV - Basement membrane
SCAB
Type I (Collagen)
- 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.
Type II (Collagen)
Cartwolage
- cartilage (including hyaline), vitreous body, nucleus pulposus
Type III (Collagen)
Deficient in vascular type of Ehlers-Danlos syndrome (threE D)
- Reticulin - skin, blood vessels, uterus, fetal tissue, early wound repair
Type IV (Collagen)
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
De Vivo Disease
(GLUT Transporter Disease)
Mutation: GLUT1
Inheritance: AD
Clinical Presentation: Seizures, Microcephaly, Motor Dysfunction
Notes:
- Low Glucose in CSF / brain
- RX: Ketogenic Diets
Pyruvate Kinase Deficiency
(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*
Pyruvate Dehydrogenase Complex ( PDHc Deficiency)
(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)
Vitamin B1 (Thiamine Pyrophosphate) Deficiency
( 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
Wet Beri Beri
( Vitamin / Coenzyme Disease)
Mutation:
- Lack B1 (Thiamine)
Inheritance:
Clinical Presentation:
- Congestive Cardiac Failure, Lactic Acidosis, peripheral Edema, Arrhythmias
Wernike’s Encephalopathy
(Vitamin / Coenzyme Disease)
“ Wet Brain Syndrome”
Mutation:
- Lack B1 (Thiamine)
Inheritance:
Clinical Presentation:
- Ataxia, Opthalmoplegia, Confusion
Notes:
- Dry Beri Beri
Vitamin B2 Deficiency (Riboflavin)
(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
Vitamin B3 Deficiency (Niacin)
( 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
Chronic Granulomatus
( 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
NADPH Oxidase Deficiency
( 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
Glucose - 6 - Phosphate- Dehydrogenase Deficiency (G6PD) Deficiency
( 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.
Von Gierke
( 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.
Anderson’s Disease
( 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
Cori Disease
( 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
McArdles Disease
(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
Her Disease
( Glycogen Metabolism Disease)
Mutation:
- Liver Glygcogen Phosphorylase
Inheritance:
Clinical Presentation:
- Hypoglycemia, Hepatomegaly
Notes:
- No liver glycogen breakdown
Pyruvate Carboxylase Deficiency
(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
Fructosuria
( Fructose Metabolism Disease)
Mutation:
- Fructokinase
Inheritance: AR
Clinical Presentation:
- Fructose in urine, UTI, dehydration
Notes:
- No fructose to F1P
Hereditary Fructose
( 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
Nonclassical Galactosemia
(Fructose Metabolism Disease)
Mutation:
- Galactokinase
Inheritance: AR
Clinical Presentation:
- Cataracts, high blood and urine galactose
Notes:
- Accumulation of galactose
Classical Galactosemia
(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.
Arsenite
( 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.
Arsenate
(Glycolysis Disease)
Mutation:
- Glyceraldehyde-3-Phospate Dehydrogenase (G3PD)
Inheritance:
Clinical Presentation:
- No second half of Glycolysis
Notes:
-Defects on G3P to 1, 3BPG
Franconi Bickel syndrome / Glycogen Storage Disease Type XI
(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.
Pompe’s Disease
(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.
Xeroderma Pigmentosum
caused by damage to XP proteins that function in nucleotide excision repair.
Ataxia Telangiectasia
caused by damage in ATM protein (cell checkpoint protein that allows entry in homologous repair pathway).
Breast/Ovarian/Prostate cancer
increased risk caused by damage to BRCA1/2 proteins (function in homologous repair pathway)
Nijmegen Breakage Syndrome
caused by defect in NBM proteins that function in repair of dsDNA.
Bloom Syndrome
caused by defect in BLM protein that regulates chromosomes; excessive sister chromatid exchange.
Werner Syndrome
caused by defect in WRN protein that regulates chromosomes and telomeres; defective base excision and homologous repair pathways.
Fanconi Anemia
caused by defect in FA proteins; leads to defective interstrand crosslink repair in chromosomes.
HPNCC/Lynch Syndrome
loss of function in mismatch repair (MSH and MLH) proteins.
Huntington’s, Fragile X, Friedriech Ataxia, Myotonic Dystrophy
STR expansions (trinucleotide repeats) caused by slippage.
Emery-Dreifuss Muscular Dystrophy
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.
Dilated Cardiomyopathy
caused by LA/C defect that cause fragile nuclear lamina, congestive heart failure, and cell death.
Lipodystrophy
caused by defects in LA/C mutation that causes accumulation of adipose in face and neck and absence in rest of body.
Hutchinson-Gilford Progeria Syndrome
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.
Spinal Muscular Dystrophy
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.
Cystic fibrosis
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.
Class I hypercholesterolemia
autosomal dominant disease caused by defects in synthesis of LDL receptor protein; inability to clear LDL and continous cholesterol synthesis.
Class II hypercholesterolemia
autosomal dominant disease caused by defects in transportation of LDL protein from RER; Class II hypercholesterolemia to clear LDL and continous cholesterol synthesis.
Class IV hypercholesterolemia
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.
I-cell disease
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.
Botulism
flaccid paralysis disease caused by neurotoxins that cleave synaptobrevin (v-SNARE for motor neurons), preventing vesicle docking and fusion of acetylcholine.
Tetanus
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.
Blistering disease/Epidermolysis Bullosa Simplex
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.
Epidermolytic Hyperkeratosis
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.
Epidermolytic Plantopalmar Keratoderma
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.
Dystrophic Epidermolysis Bullosa
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.
Kwashiorkor
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
Marasmus
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
Vitamin B5 (Pantothenate)
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
Vitamin B6 (Pyridoxine)
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
Vitamin B12 (Cobalamin)
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
- paresthesias and subacute combined degeneration
- 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
Folic Acid
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
Biotin
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
Vitamin C (Ascorbic Acid)
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)
S-Adenosylmethionine (SAM)
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
Lysosomal Storage Disease (by Deficient Enzymes)
Sphingomyelinase
Sphingolipidoses
- deficient in Niemann-Pick disease
- sphingomyelin accumulates
- histiocytes look “foamy”
- sphingomyelin accumulates
Clinical presentation:
hepatosplenomegaly
anemia
cherry red spots on macula
death < 3 years
failure to thrive
neurodegeneration
inheritance:
AR
risk ↑ in Ashkenazi Jews
Lysosomal Storage Disease (by Deficient Enzymes)
α-galactosidase 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
Lysosomal Storage Disease (by Deficient Enzymes)
β-galactocerebrosidase
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
Lysosomal Storage Disease (by Deficient Enzymes)
β-glucocerebrosidase
2nd Disease
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
Lysosomal Storage Disease (by Deficient Enzymes)
Arylsulfatase A
Sphingolipidoses
deficient in metachromatic leukodystrophy
cerebroside sulfate accumulates
Clinical presentation:
demyelination in CNS and PNS
resulting in ataxia and dementia
inheritance:
AR
Lysosomal Storage Disease (by Deficient Enzymes)
α-L-iduronidase
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
Lysosomal Storage Disease (by Deficient Enzymes)
Iduronate sulfatase
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
