ALL BIOCHEM IN FIRST AID Flashcards
1
Q
ADA DEFICIENCY
A
ADA—require for degradation of adenosine and deoxyadenosine
Increased levels of dATP—> leads to lymphotoxicity
One of the major causes of AR SCID
2
Q
LESCH-NYHAN SYNDROME
A
Defective purine salvage due to absent HGPRT
(Converts hypoxanthine to IMP and guanine to GMP)
Results:
Excess Uric acid production
X—linked Recessive
Findings: intellectual disability, SELF-MUTILATION, aggression, hyperuricemia (orange “sand” in diaper), gout, dystonia
TX:
Allopurinol
Febuxostat (2nd line)
3
Q
XERODERMA PIGMENTOSUM
A
Defective nucleotide excision repair —> inability to repair DNA pyrimidine dimers caused by UV exposure Findings: Dry skin Extreme light sensitivity Skin cancer
4
Q
I-CELL DISEASE (INCLUSION CELL DISEASE)
A
Inherited lysosomal storage disorder
Defect in—> N-acetylglucosaminyl-1-phosphotransferase
Failure of the Golgi to phosphorylate mannose residues (DECREASE mannose-6-phosphate)
Proteins are secreted extracellularly rather than sent to lysosomes
Findings: Coarse facial features Gingival hyperplasia Clouded corneas Restricted joint movements Claw hand deformities Kyphoscoliosis High plasma levels of lysosomal enzymes FATAL IN CHILDHOOD
5
Q
ZELLWEGER SYNDROME
A
AR Mutated PEX genes—leads to peroxisome biogenesis disorder Findings: Hypotonia Seizures Hepatomegaly Early death
6
Q
REFSUM DISEASE
A
AR of alpha-oxidation Findings: Scaly skin Ataxia Cataracts/night blindness Shortening of 4th toe Epiphyseal dysplasia TX: Diet, plasmapheresis
7
Q
ADRENOLEUKODYSTROPHY
A
X-linked Recessive disorder of BETA-oxidation
VLCFA buildup in adrenal glands, white matter of brain, testes
8
Q
KARTAGENER SYNDROME
A
Immobile cilia due to a dynein arm defect AR Results: Decrease in male/female fertility due to immotile sperm and dysfunctional Fallopian tube cilia Increased risk of ectopic pregnancy Can cause: Bronchiectasis Recurrent sinusitis Chronic ear infections Conductive hearing loss Situs inversus (dextrocardia on CXR)
9
Q
OSTEOGENESIS IMPERFECTA “Brittle Bone Disease”
Type 1 = Mild
Type 2 = severe and usually lethal in peri-natal period (die due to respiratory failure (pulmonary hypoplasia) or intra-cerebral hemorrhage)
Type 3 = considered progressive and deforming
Type 4 = deforming but with NORMAL sclera
A
Genetic bone disorder: variety of gene defects in COL1A1 or COL1A2–MC form is AD with decreased production in TYPE 1 collagen
Impaired osteioid production by osteoblasts
Genetic mutation causing alpha peptides deficient in glycine
Problems forming triple helix due to defect in glycosylation
Findings:
Multiple fractures with minimal trauma (may occur during the birth process)
Blue sclera due to translucent CT over choroidal veins
Opalescent teeth that wear easily due to lack of dentin
Hearing loss
TX:
Bisphosphonates to decrease fracture risk
10
Q
EHLERS-DANLOS SYNDROME:
Classical Type:
Type V collagen mutation—joint and skin sx.
Vascular Type:
Deficient type III pro-collagen (problems with cleavage)
Fragile tissues including vessels, muscles, and organs
A
Faulty collagen synthesis causing: Hyperextensible skin Hyper mobile joints Tendency to bleed (easy bruising) Can be AD or AR Associated with: Joint dislocation Berry and aortic aneurysms Organ rupture *Hypermobility is the MC type*
11
Q
MENKES DISEASE
A
X-linked R Cause: Impaired copper absorption and transport due to defective Menke’s protein ATP7A Leads to—> decreased activity of lysyl oxidase—> defective collagen Results: “Brittle, kinky” hair Growth retardation Hypotonia
12
Q
MARFAN SYNDROME
A
AD disorder affecting skeleton, heart and eyes
FBN1 gene mutation on chromosome 15–defective fibrillin
Findings: Tall with long extremities Pectus carinatum or pectus excavatum Hyper mobile joints Long, tapering fingers and toes Cystic medial necrosis of aorta*** aortic incompetence, dissecting aortic aneurysms Floppy mitral valve Subluxation of lenses** typically upward/temporally
13
Q
PCR
A
Used to amplify a desired fragment of DNA
Useful as a diagnostic tool
(1) Denaturation (heat)
(2) Annealing (cool + DNA primers)
(3) Elongation (heat)
—looking for a specific sequence for illness or mutation
14
Q
Southern Blot
A
DNA sample is cleaved
Put onto a gel then transferred to a filter
Filter is exposed to radiolabeled DNA probe
Resulting DS, labeled DNA is visualized when filter is exposed to film
**Unknown sample
**Used for forensics
15
Q
Northern Blot
A
RNA sample is electrophoresis
Useful for studying mRNA levels, which are reflective of gene expression
Detects RNA using a DNA probe
16
Q
Western Blot
A
Sample protein is separated via gel electrophoresis and transferred to a membrane
Labeled antibody is used to bind to relevant protein** HIV test screening test
17
Q
Southwestern Blot
A
Identifies DNA-binding proteins using labeled oligonucleotide probes
18
Q
Flow Cytometry
A
To assess size, granularity, and protein expression (immunophenotype) of individual cells in a sample
FOR: workup of hematologic abnormalities and immunodeficiencies
Cells tagged with antibodies specific to surface or intracellular proteins
Antibodies then tagged with a unique fluorescent dye
19
Q
Microarrays
A
Used to look @ entire genome
DNA or RNA probes are hybridized to the chip and a scanner detects the relative amounts of complementary binding
Able to detect SNP’s and CNV’s for a variety of applications: Genotyping Clinical genetic testing Forensic analysis Cancer mutations Genetic linkage analysis
20
Q
ELISA
A
Immunologic test used to detect the presence of either a specific antigen or antibody in a patient’s blood sample
Initial test for HIV: confirmed with Western Blot
Direct ELISA—> tests for the antigen directly
Indirect ELISA—> tests for the antibody (thus indirectly testing for the antigen)
21
Q
Karyotyping
A
Used to diagnose chromosomal imbalances
Can be performed on: sample of blood, bone marrow, amniotic fluid or placental tissue
Metaphase chromosomes are used
22
Q
FISH
A
Fluorescent DNA or RNA probe binds to specific gene site of interest on chromosomes
Used for: specific localization of genes and direct visualization of chromosomal anomalies at the molecular level
23
Q
MCCUNE-ALBRIGHT SYNDROME
A
Mutation affecting G-protein signaling
Presents with:
Unilateral cafe-au-lait spots with ragged edges
Polyostotic fibrous dysplasia (bone replaced by collagen and fibroblasts)
Precocious puberty
Lethal if mutation occurs BEFORE fertilization but survivable in patients with mosaicism
24
Q
PRADER-WILLI SYNDROME
A
Paternal allele is deleted/mutated Maternally derived genes are silenced (imprinted) **Mutation or deletion of chromosome 15 of PATERNAL origin Results: Hyperphagia (excessive eating) Obesity Intellectual disability Hypogonadism Hypotonia
25
ANGELMAN SYNDROME
Paternally derived UBE3A gene is silenced
Maternal allele is deleted or mutated
**maternal copy of chromosome 15 deleted*
```
Results:
Inappropriate laughter
Seizures
Ataxia
Severe intellectual disability
```
26
Mitochondrial Myopathies
```
Often present with:
Myopathy
Lactic acidosis
CNS disease
[MELAS syndrome]
Mitochondrial encephalomyopathy
Lactic acidosis
Stroke-like episodes
```
Secondary to oxphos failure
Muscle biopsy = ragged red fibers due to accumulation of disease mitochondria
27
CYSTIC FIBROSIS
Dx: Increased Cl- concentration in pilocarpine-induced sweat test
Increased trypsinogen (newborn screening)
TX: Azithromycin (anti-inflammation) Ibuprofen slows disease progression**
In patients with deletion: lumacaftor (corrects misfolded proteins) + ivacaftor (opens CL- channels)
AR
Defect in CFTR gene on chromosome 7
Deletion of Phe508
MC lethal genetic disease in Caucasian’s
CFTR—> encodes ATP-gated Cl- channel that secretes Cl- in lungs and GI tract and reabsorbs Cl- in sweat glands
MC mutation = misfolded protein that is retained in the RER causing decreased CL- secretion; increased intracellular Cl- results in compensatory increased Na+ reabsorption via ENAC channels which increases H20 reabsorption =
ABNORMALLY THICK MUCUS
28
CF complications
Recurrent pulmonary infections (Staph in early infancy, Pseudomonas in adolescence)
Chronic bronchitis and bronchiectasis
(Reticulo-nodular on CXR)
Pancreatic insufficiency
Malabsorption with steatorrhea, fat-soluble vitamin deficiencies, biliary cirrhosis, liver disease
Meconium ileus in newborns**
Infertility in men (absence of vas deferens) and sub-fertility in women
Nasal polyps, clubbing of nails
29
DUCHENNE MUSCULAR DYSTROPHY
Dystrophin—> connects the intracellular cytoskeleton (actin) to the transmembrane proteins alpha and beta-dystroglycan which are connected to the ECM
Increased CK and Aldolase
X-linked disorder typically due to frameshift or nonsense mutations—> truncated or absent dystrophin—> progressive myofiber damage
Weakness begins in pelvic girdle muscles and progresses superiorly
**Pseudohypertrophy of calf muscles + waddling gait**
Onset before 5 years of age—dilated cardiomyopathy is MC COD
GOWER SIGN = use UE to help stand up
30
BECKER MD
X-linked disorder due to NON-frameshift deletions in dystrophin gene
Onset in adolescence or early adulthood (partially functional dystrophin)
31
MYOTONIC TYPE 1 MUSCULAR DYSTROPHY
AD
CTG trinucleotide repeat expansion in the DMPK gene—> abnormal expression of myotonin protein kinase
```
SX:
Myotonia
Muscle wasting
Cataracts
Testicular atrophy
Frontal balding (early balding in men)
Arrhythmias
```
32
RETT SYNDROME
Sporadic disorder seen almost exclusively in girls
Caused by de novo mutation of MECP2 on X chromosome
```
SX:
Usually appear between ages 1-4
Regression in motor, verbal, and cognitive abilities
Ataxia
Seizures
Growth failure
Stereotyped hand-wringing**
```
33
FRAGILE X SYNDROME
X-linked dominant
Trinucleotide repeat (CGG) in FMR1–> hypermethylation—> decreases expression
MC cause of inherited intellectual disability
```
SX:
Post-pubertal macroorchidism
Enlarged testes
Long face with a large jaw
Large exerted ears
Autism
MVP
```
34
DOWN SYNDROME (TRISOMY 21)
```
Intellectual disability
Flat facies
Prominent epicanthal folds
Single palmar crease
Gap between 1st two toes
Duodenal atresia
Hirschsprung disease
Congenital heart disease
Brushfield spots (grayish brown spots on iris)
Associations: early onset Alzheimer disease and increased risk of ALL and AML
```
95% due to meiotic nondisjunction
4% due to Robertsonian translocation between 14 and 21
```
Tests:
Decreased PAPP-A
Increased beta-HCG
Decreased AFP
Decreased estriol
Increased inhibin
```
35
EDWARDS SYNDROME (TRISOMY 18)
```
FINDINGS:
Prominent occiput
Rocker-bottom feet
Intellectual disability
Non-disjunction
Clenched fists
Low-set ears
Micrognathia (small jaw)
Congenital heart disease
Death by age 1
Labs: < beta-HCG, < AFP, < estriol, normal or < inhibin
```
36
PATAU SYNDROME (TRISOMY 13)
```
Findings:
Severe intellectual disability
Rocker-bottom feet
Microphthalmia
Microcephalic
Cleft lip-cleft palate
Holoprosencephaly
Polydactyly
Cutis aphasia
Congenital heart disease
Polycystic kidney disease
Death by age 1
Labs: < beta-HCG, normal everything else
```
37
CRI-DU-CHAT SYNDROME
Congenital deletion on short arm of chromosome 5
```
Findings:
Microcephalic
Moderate to severe intellectual disability
High-pitched cry, “meowing”
Epicanthal folds
VSD
```
38
WILLIAMS SYNDROME
Congenital micro-deletion of long arm of chromosome 7 (deleted region includes elastin gene)
```
Findings:
“Elfin” facies
Intellectual disability
HyperCa2+
Well—developed verbal skills
Extreme friendliness with strangers
CV problems
```
39
22q11 Deletion Syndrome-DiGeorge Syndrome (thymic, parathyroid, cardiac defects)—Velo-cardiofacial syndrome (palate, facial, cardiac defects)
DUE TO: aberrant development of 3rd and 4th branchial (pharyngeal) pouches
```
Microdeletion at chromosome 22q11
Presentation variable:
Cleft palate
Abnormal facies
Thymic aplasia—> T-cells deficiency, cardiac defects, HypoCa2+ to parathyroid aplasia
```
40
VITAMIN A
[RETINOL]
Uses:
Prevents squamous metaplasia
TX: measles and APL (M3); severe cystic acne; wrinkles
```
Deficiency:
Night blindness
Dry scaly skin
Corneal degeneration
Bigot spots (foamy appearance) on conjunctiva
Immunosuppression
```
EXCESS:
Acute toxicity—> N/V, vertigo, blurred vision
Chronic toxicity—> alopecia, dry skin, hepatic toxicity and enlargement, arthralgias, and pseudotumor cerebri
TERATOGENIC—> must have a - pregnancy test and be on two forms of BC before prescribed isotretinoin
41
VITAMIN B1
[THIAMINE]
Uses:
Used in several dehydrogenase reactions:
(1) Pyruvate dehydrogenase
(2) alpha-ketoglutarate dehydrogenase
(3) transketolase
Cause of Wernicke-Korsakoff Syndrome:
confusion + ophthalmoplegia + ataxia + confabulation + personality change + memory loss (damage to medial dorsal nucleus of thalamus, mammillary bodies)
(4) branched chain keto-acid dehydrogenase
Deficiency:
Impaired glucose breakdown—> ATP depletion worsened by glucose infusion; highly aerobic tissues are affected first
Give thiamine before dextrose in alcoholic patients to decrease risk of causing Wernicke’s
DX: increase in RBC transketolase activity following B1 administration
42
BERIBERI
```
“DRY”
Polyneuropathy
Symmetrical muscle wasting
“WET”
High-output cardiac failure (dilated cardiomyopathy)
Edema
```
43
VITAMIN B2
[RIBOFLAVIN]
Component of FAD and FMN (used in redox reactions)
DEFICIENCY:
Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
Corneal vascularization
44
VITAMIN B3
```
[NIACIN]
Uses:
NAD+, NADP+
Derived from tryptophan
TX: dyslipidemia—> lowers levels of VLDL and raises levels of HDL
```
DEFICIENCY
Glossitis
Severe deficiency leads to PELLAGRA: can be caused by:
Hartnup disease
Malignant carcinoid syndrome (increased tryptophan metabolism)
Isoniazid**
```
SX: “the three D’s”
Diarrhea
Dementia
Dermatitis “broad collar rash”
Hyperpigmentation of sun-exposed limbs
```
EXCESS: “PODAGRA”
Facial flushing—avoid by taking aspirin
Hyperglycemia
Hyperuricemia
45
HARTNUP DISEASE
AR
Deficiency of neutral amino acid (tryptophan) transporters in proximal renal tubular cells and on enterocytes
Neutral aminoaciduria and decreased absorption from the gut causes decreased tryptophan to be converted into niacin = PELLAGRA
TX: high protein diet + nicotinic acid
46
VITAMIN B5
[PANTOTHENIC ACID]
Essential component of CoA and fatty acid synthase**
```
DEFICIENCY:
Dermatitis
Enteritis
Alopecia
Adrenal insufficiency
```
47
VITAMIN B6
```
[PYRIDOXINE]
Synthesis of:
Cystathionine
Heme
Niacin
Histamine
NT (serotonin, EPI, NE, dopamine, GABA)
```
DEFICIENCY:
Convulsions
Hyperirritability
Peripheral neuropathy (because needed for myelin)
Sideroblastic anemia (due to impaired hemoglobin synthesis)
Can be induced by:
Isoniazid and OC
48
VITAMIN B7
[BIOTIN]
Cofactors for carboxylation enzymes:
Pyruvate carboxylase (pyruvate—> oxaloacetate)
Acetyl-CoA carboxylase (acetyl-CoA—> malonyl CoA)
Propionyl-CoA carboxylase (propionyl-CoA—> methylmalonyl-CoA)
DEFICIENCY:
Caused by antibiotic use or excessive ingestion of raw egg whites **
49
VITAMIN B9
[FOLATE]
Converted to THF
Important for synthesis of RNA and DNA nitrogenous bases
Stored primarily in liver
```
DEFICIENCY:
Megaloblastic macrocytic anemia
No neuro SX.
Labs:
Increased homocysteine
Normal MMA
```
**Seen in alcoholism and pregnancy
Can be caused by: phenytoin, sulfonamides, MTX
Supplemental maternal folic acid at least 1 month prior to conception and during early pregnancy decreases risk of NTD
50
VITAMIN B12
[COBALAMIN]
Cofactor for methionine synthase and MM-CoA mutase—important in DNA synthesis
Stored in liver—very large reserve pool
```
DEFICIENCY:
Macrocytic, megaloblastic anemia
Paresthesias and subacute combined degeneration (degeneration of dorsal columns, lateral CST, and spinocerebellar tracts) due to abnormal myelin
Labs:
Increased homocysteine
Increased MMA
```
```
Caused by:
Malabsorption
Achlorhydria
Bacterial overgrowth
Alcohol excess
Lack of IF
Absence of terminal ileum (CD)
Insufficient intake
```
**Anti-IF antibodies dx for pernicious anemia
51
VITAMIN C
[ASCORBIC ACID]
Facilitates iron absorption by reducing it to Fe2+
Hydroxylation of proline and lysine in collagen synthesis
For dopamine hydroxylase which converts dopamine to NE
tx for methemoglobinemia
DEFICIENCY = SCURVY
Swollen gums + bruising + petechiae + hemarthrosis + anemia + poor wound healing + peri-follicular and sub-periosteal hemorrhage’s + “corkscrew hair”
EXCESS:
N/V/D, fatigue, Ca2+ stones, can worsen iron toxicity
52
VITAMIN E
Protects RBC and membranes from free radical damage
Enhances anticoagulant effects of warfarin by altering vitamin K metabolism
```
Deficiency:
Hemolytic anemia
Muscle weakness
Acanthocytosis
Posterior column/spinocerebellar tract demyelination
```
53
KWASHIORKOR
Protein malnutrition resulting in skin lesions, edema due to decreased plasma oncotic pressure, liver malfunction
Clinical picture:
Small child + swollen abdomen
From protein deficiency meals
54
MARASMUS
Malnutrition not causing edema
Diet is deficient in calories but no nutrients are entirely absent
*Muscle wasting
55
Fomepizole
Inhibits alcohol dehydrogenase
| Antidote for overdoses of methanol or ethylene glycol**
56
Disulfiram
Inhibits acetylaldehyde dehydrogenase (acetylaldehyde accumulates)
Discouraging drinking
57
PYRUVATE DEHYDROGENASE DEFICIENCY
X-linked
Causes a buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT)
Findings:
Neuro defects
Lactic acidosis
Increased serum alanine
TX:
Increase intake of ketogenic nutrients = high fat content or increased lysine and leucine
58
G6PD DEFICIENCY
X-Linked recessive
NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides
Decreased NADPH in RBC’s leads to hemolytic anemia due to poor RBC defense against oxidizing agents
Infection (MC cause), can precipitate hemolysis
> in AA, increased malarial resistance
Heinz bodies and bite cells = path
59
ESSENTIAL FRUCTOSURIA
AR
Defect in FRUCTOKINASE
Benign, asymptomatic condition since fructose is NOT trapped in cells
Sx:
Fructose appears in the urine and blood
60
HEREDITARY FRUCTOSE INTOLERANCE
AR
Deficiency of ALDOLASE B
Fructose-1-phosphate accumulates, causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis
Sx:
Present with consumption of fruit, juice or honey
Reducing sugar found in urine
Hypoglycemia, jaundice, cirrhosis, vomiting, abnormal LFT’s
TX: decrease intake of both fructose and sucrose (glucose + fructose)
61
GALACTOKINASE DEFICIENCY
AR
Hereditary deficiency of GALACTOKINASE
Galactitol accumulates if galactose is present in diet
Sx:
Galactose appears in blood and urine
Infantile cataracts
Failure to track objects or to develop a social smile
62
CLASSIC GALACTOSEMIA
AR
Absence of GALACTOSE-1-PHOSPHATE URIDYLTRANSFERASE
Damage is caused by accumulation of toxic substances
```
SX:
Develop when infant begins feeding and include:
Failure to thrive
Jaundice
Hepatomegaly
Infantile cataracts
Intellectual disability
Predispose to E.Coli sepsis in infants
```
TX:
Exclude galactose and lactose from diet
63
SORBITOL DEHYDROGENASE DEF
Intracellular sorbitol accumulation
Causing:
Osmotic damage (cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in diabetes)
64
LACTASE DEFICIENCY
Dietary lactose intolerance
(Functions on the intestinal brush border to digest lactose)
Primary: age-dependent decline after childhood
Secondary: loss of intestinal brush border due to gastroenteritis, autoimmune disease
```
Stool demonstrates:
Decreased pH
Breath has increased H+ content with lactose hydrogen breath test
Intestinal biopsy:
Normal mucosa**
```
Findings:
Bloating
Cramps, flatulence
Osmotic diarrhea
TX: avoid dairy products or add lactase pills to diet
65
HYPERAMMONEMIA
Can be acquired (liver disease) or hereditary (urea cycle enzyme deficiencies)
Excess NH3–> depletes GABA in the CNS and alpha-ketoglutarate inhibiting the TCA cycle
TX: limit protein in the diet
Lactulose—> acidifying the GI tract and trapping NH4+ for secretion
Antibiotics to decrease ammoniagenic bacteria
Benzoate, phenylacetate, or phenylbutyrate react with glycine or glutamine, forming products that are really excreted
```
SX:
Flapping tremor (asterixis)
Slurring of speech
Somnolence
Vomiting
Cerebral edema
Blurring of vision
```
66
ORNITHINE TRANSCARBAMYLASE DEFICIENCY
| Ornithine—> citrulline
X-linked recessive
Interferes with the body’s ability to eliminate ammonia
Evident in the 1st few days of life
Findings:
Increased orotic acid in blood/urine, decreased BUN
67
PHENYLKETONURIA
AR—screened 2-3 days after birth
Decreased phenylalanine hydroxylase or decreased BH4 cofactor
Increased phenylalanine causes excess phenyl ketones in the urine
```
SX:
Intellectual disability
Growth retardation
Seizures
Fair complexion
Eczema
Musty body odor
```
TX: decrease phenylalanine and increase tyrosine in the diet. BH4 supplementation; avoid aspartame
68
MAPLE SYRUP URINE DISEASE
AR
Blocked degradation of branched amino acids (isoleucine, valine, leucine) due to DECREASED branched-chain alpha-ketoacid dehydrogenase
```
SX:
Severe CNS defects
Intellectual disability
Death
vomiting
Poor feeding
Urine smells like maple syrup/burnt sugar
```
TX: restriction of isoleucine, leucine, valine in diet and thiamine supplementation
69
ALKAPTONURIA “BLACK URINE DISEASE”
AR
Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
Homogentisic acid accumulates in tissue
SX:
Bluish-black CT, ear cartilage, sclera
Urine turns black on prolonged exposure to air
Debilitating arthralgias
70
HOMOCYSTINURIA
AR
```
All forms SX:
Increased homocysteine in urine
Osteoporosis
Marfan oil habitus
Ocular changes (downward and inward)
CV affects
Kyphosis
Intellectual disability
```
71
CYSTINURIA
AR
Hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine (COLA)
Excess cystine in the urine can lead to recurrent precipitation of HEXAGONAL cystine stones
TX:
Urinary alkalinzation
Chelating agents (pencillamine)
Dx: urinary cyanide-nitroprusside test
72
VON GIERKE DISEASE (TYPE 1 GLYCOGEN STORAGE DISEASE)
| PAS + = glycogen in cells
Deficient in Glucose-6-phosphatase
```
Sx:
Severe fasting hypoglycemia
Increased glycogen in liver and kidneys
Increased blood lactate
Increased TG’s
Increased Uric acid (gout)
Hepatorenomegaly
```
TX:
Frequent oral glucose/cornstarch
Avoidance of fructose/galactose
73
POMPE DISEASE (TYPE II)
Def in lysosomal acid alpha 1-4-glucosidase with alpha 1-6 glucosidase activity
```
Sx:
Cardiomegaly
Hypertrophic cardiomyopathy
Hypotonia
Exercise intolerance
Lead to early death
```
74
CORI DISEASE (TYPE III)
Def: debranching enzyme (alpha-1,6 glucosidase)
Milder form of Von GIERKE with normal blood lactate levels
Accumulation of limit dextrin-like structures in cytosol
75
MCARDLE DISEASE (TYPE V)
Def: skeletal muscle glycogen phosphorylase
HALLMARK = flat venous lactate curve with normal rise in ammonia levels during exercise
Blood glucose levels typically unaffected
Sx:
Increased glycogen in muscle
Painful muscle cramps**
Myoglobinuria (red urine)** with strenuous exercise
Arrhythmia from electrolyte abnormalities
Decreased exercise tolerance
76
TAY SACHS DISEASE
AR
Def: Hexoaminidase A
Accumulated = GM2 ganglioside
```
SX:
Progressive neurodegeneration
Developmental delay
“Cherry-red” spot on macula
Lysosomes with onion skin
NO HSM
```
77
FABRY DISEASE
XR
Def: alpha-galactosidase A
Accumulation = ceramide trihexoside
SX:
Early: triad of episodic peripheral neuropathy + angiokeratomas (lesion of capillaries) + hypohidrosis (complete absence of sweating)
Late: progressive renal failure + CV disease
78
METACHROMATIC LEUKODYSTROPHY
AR
Def: Arylsulfatase A
Accumulation = cerebroside sulfate
SX:
Central and peripheral demyelination with ataxia, dementia
79
KRABBE DISEASE
AR
Def: Galactocerebrosidase
Accumulation = galactocerebroside, psychosine
```
SX:
Peripheral neuropathy
Destruction of oligodendrocytes
Developmental delay
Optic atrophy
Globoid cells
```
80
GAUCHER DISEASE
AR
Def: Glucocerebrosidase
Accumulation = Glucocerebroside
```
SX:
MC
HSM
Pancytopenia
Osteoporosis
Avascular necrosis of femur
Bone crises
GAUCHER cells = crumpled tissue paper; lipid-laden macrophages
```
81
NIEMANN-PICK DISEASE
AR
Def: Sphingomyelinase
Accumulation = sphingomyelin
```
SX:
Progressive neurodegeneration
HSM
Foam cells
Cherry red spot on macula
```
82
HURLER SYNDROME
AR
Def: alpha-L-iduronidase
Accumulation = heparan sulfate, dermatan sulfate
```
SX:
Developmental delay
Gargoyles (thickened gums, upturned nose)
Airway obstruction
Corneal clouding
HSM
```
83
HUNTER SYNDROME
XR
Def: Iduronate-2-sulfatase
Accumulation = heparan sulfate, dermatan sulfate
SX:
Mild hurler
Aggressive behavior
NO corneal clouding
84
ABETALIPOPROTEINEMIA
AR
Chylomicrons, VLDL, LDL absent
Deficiency in APO B-48 and APO B-100
Present with:
Severe fat malabsorption
Steatorrhea
Failure to thrive
```
Later manifestations:
Retinitis Pigmentosum
Spinocerebellar degeneration due to vitamin E deficiency
Progressive ataxia
Acanthocytosis
```
TX: restrict long chain fatty acids, large doses of oral vitamin E
85
HYPERCHYLOMICRONEMIA-TYPE 1 DYSLIPIDEMIA
AR
Lipoprotein lipase or apolipoprotein C-II deficiency
Increase blood chylomicrons, TG and cholesterol
```
SX:
Pancreatitis
HSM
Eruptive/pruritic xanthomas
Creamy layer in supernatant
```
86
FAMILIAL HYPERCHOLESTEROLEMIA-TYPE II DYSLIPIDEMIA
AD
Absent or defective LDL receptors or defective ApoB-100
Increased LDL, cholesterol and in type IIB also VLDL
SX:
Accelerated atherosclerosis (may have MI before 20)
Tendon xanthomas
Corneal arcus—white, grey or blue opaque ring in the corneal margin
87
DYSBETALIPOPROTEINEMIA-TYPE III DYSLIPIDEMIA
AR
Defective ApoE
Increased chylomicrons and VLDL
SX:
Premature atherosclerosis
Tuberoeruptive xanthomas
Palmar xanthomas
88
HYPERGTRIGLYCERIDEMIA-TYPE IV DYSLIPIDEMIA
AD
Hepatic overproduction of VLDL
Increased VLDL, TG
SX:
Hypertriglyceridemia may cause acute pancreatitis
Related to insulin resistance
