Autosomal Recessive Cause Clinical Presentation Test Treatment

Cystic Fibrosis Deletion ΔF508 gene -Obstructive lung disease, lung infections, malabsorption (pancreatic -Axillary Sweat
Mutation in CFTR: Cl ion channel (plasma transmembrane insufficiency), salty sweat, male infertility Test
protein in epithelial cells) -incorrect protein folding which gets -Meconium Ileus -ASO
-Anemia
degraded
Spinal Muscular Atrophy -Mutation in Gems containing SMN Protein (survival of motor -Sudden onset – rapid progression
neurons) causes defective snRNP assembly, which causes -Muscle weakness & atrophy
defective Pre-mRNA splicing -Hypotonia
-loss of motor neurons (in spinal cord & brainstem) -Dysphagia & feeding difficulties
-Respiratory problems
I-cell -Deficiency of N-acetylglucosamine (GlcNAc) -Coarse Facial features
phosphotransferase in cis-Golgi fails to phosphorylate mannose -Clouded corneas
(Mucolipidosis II) residues for M6P signal. -Increased plasma levels of lysosomal enzymes
-Intracellular accumulation of substance in lysosomes – I cells -Restricted joint movements
-Psychomotor retardation; enlarged liver, spleen, heart, valves
-Life expectancy <10yrs
Pseudo-Hurler -Failure of N-acetylglucosamine phosphotransferase in cis- -Later onset
Golgi fails to make the M6P signal. -Survival into adulthood
Polydystrophy -Milder form of I-cell
(Mucolipidosis III) -Mucopolysaccharidoses (accumulation of sulfated
polysaccharides/GAGs)
Hurler Syndrome -Deficiency of α-L-iduronidase, which causes accumulation of -Initially normal growth (growth stops 2-4 yrs.) -Enzyme
dermatan sulphate & heparan sulphate. -Problems begin at a few months old therapies
(Mucolipidosis IH) -Mucopolysaccharidoses (accumulation of sulfated -physical & mental deterioration
polysaccharides/GAGs) -Deafness, skeletal deformity (Dysostosis multiplex), coarse
-GAG storage within blood vessels causes irregular & diffuse features,
narrowing of the coronary arteries. -Hirsutism (lots of hair)
-Corneal clouding
-Death <10 years
Scheie -Deficiency of α-L-iduronidase, which causes accumulation of -Mildest type of MPS I
dermatan sulphate & heparan sulphate. Residual enzyme -Onset after age 5, normal lifespan
(Mucolipidosis IS) activity -Normal intelligence,
-Mucopolysaccharidoses (accumulation of sulfated -corneal clouding
polysaccharides/GAGs) -Valvular heart disease
Morquio Syndrome -N-acetylgalactosamine-6-sulfatase deficiency affects Keratan -Skeletal abnormalities: bell-shaped chest, spine flattening of
sulfate degradation (cartilage & cornea). curvature, shortened long bones, dysplasia of hips, knees, ankles,
(MPS IV) wrists.
-Cardiac & dental abnormalities
-Deafness & corneal opacification
Tay-Sachs -Accumulation of gangliosides (GM2) -Rapid and progressive neurodegeneration
-blindness
-Cherry-red macula
-muscular weakness
-seizures
Metachromatic -Deficiency of ARSA (Arylsulfatase A)
-Defective degradation of sulfatides (galactocerebroside-3-
Leukodystrophy sulfate & derivatives)
-Accumulation of sulfatides in cells=toxic to CNS; destruction of
myelin on oligodendrytes
-Progressive leukodystrophy in CNS--> PNS
Chediak-Higashi Syndrome -Rare Lysosomal disorder
-Involves CHS1/LYST gene, encoding a lysosomal trafficking
regulatory protein that normally induces vesicle fusion:
-Delayed fusion of phagosome with lysosomes in leukocytes
-Autophagocytosis of melanosomes in melanocytes
-Granular defects in NK & Platelets
Zellweger Syndrome - failure to import peroximal enzymes due to membrane not
recognizing the localization aa signal used to import peroximal
proteins which empty peroxisomes
-Peroxisome deficiency (VLCFA accumulates in blood & tissues,
lack of plasmalogen- (abnormalities in nerve cell myelination))
Primary Ciliary Dyskinesia -Dynein is not functional causing Immotile cilia & sperm cause
retention of secretions & recurrent infections.
(PCD) (50% have Kartagener Syndrome)
Kartagener Syndrome -Nodal cilia help drive flow of "packets" of sonic hedgehog (a
protein) and retinoic acid (an organic chemical related to
Vitamin A) both of which are morphogens which are important
for embryonic development.
Dystrophic Epidermolysis -Mutation in Collagen VII (absence of anchoring fibrils)
-Most severe & debilitating of the blistering disorders.
Bullosa (Relatively mild presentation is possible)
(3 types EB: Dystrophic, Junctional, Simplex)
(Can also be Autosomal Dominant)
Junctional Epidermolysis Mutation in laminin, integrins or hemidesmosomal proteins
Bullosa
(3 types EB: Dystrophic, Junctional, Simplex)
Fanconi Bickel Syndrome -Mutation in the GLUT2 transporter –impared transport of
glucose, galactose, & fructose
-hepatorenal glycogen accumulation & proximal renal tubular
dysfunction-
Congenital (Autosomal Recessive)
-absent lactase, normal histology
Primary (not genetically inherited)
-genetically regulated reduction of lactase enzyme activity
Lactose Intolerance -low intestinal lactase activity by school age
(Congenital, primary, secondary)
-Cognitive deterioration
-Demyelination
-Progressive paralysis
-Dementia in adult form
-Nerves stain yellowish-brown with cresyl violet (metachromasia)
-gait disturbance, progressive loss of muscle tone
-Juvenile form (onset 4-13 yrs 20-30%)
-Adult form (onset teenage yrs or later 20%) -behavioral problems,
(alcoholism, drug abuse) psychiatric symptoms (delusions,hallusinations), survival 20-
30yrs.
-Albinism/hypopigmentation/silvery hair -Bone marrow
-Recurrent infections (life threatening) txp
-eyes sensitive to sunlight
-Neutropenia & bruising develop over time
-Coagulation defects
-May develop neuropathy and ataxia
-Abnormal brain development due to VLCFA accumulation in glial
cell membrane (no β-oxidation)
-Hepatomegaly & liver failure – accumulation of VLCFAs in liver
-Decreased fat absorption (lack of bile acids)
-Muscle weakness (lack of plasmalogen)
-Recurrent infections such as bronchitis, otitis media & sinusitis.
-Infertility
-Bronchiectasis
-Situs inversus (organs are organized “opposite to normal”)
-Chronic paranasal sinusitis
-Infertility
-down deep, skin falls off causing syndactyly & scarring
-Skin blisters very easily
-Mucosa becomes involved in severe forms
-down deep, skin falls off causing syndactyly & scarring
-Skin blisters very easily
-Failure to thrive
-Hepatomegaly (secondary to glycogen accumulation)
-Vit D resistant rickets- the bones become painfully soft and bend easily, due to
low levels of phosphate in the blood
-Fasting ketotic hypoglycemia & postprandial Hyperglycemia due to
the low hepatic uptake of glucose
-Diarrhea from birth -Lactose
- abdominal pain, flatulence, nausea, bloating, and diarrhea after tolerance test
ingestion of milk or milk-containing products -Breath
-abdominal pain, flatulence, nausea, bloating, and diarrhea after hydrogen test
ingestion of milk or milk-containing products -Stool acidity
test: pH &
 Secondary (not genetically inherited) -abdominal pain, flatulence, nausea, bloating, and diarrhea after amount of
-Intestinal diseases which affect large areas of the mucosal ingestion of milk or milk-containing products sugars in stool
surface, which result in decrease of digestive activity. -Small bowel
biopsy
-Genetic test
Pyruvate Kinase Deficiency -Second most common cause for enzyme deficiency related -Anemia -Peripheral
hemolytic anemia (first –G6PD deficiency) -Splenomegaly smear-
-accumulation of substrates proximal to pyruvate kinase – -Jaundice - (increase in unconjugated bilirubin) hedgehog
decrease in lactate & ATPs in RBCs -Pigment gall stones – Precipitation of bilirubin shaped
-Decreased ATP-Inhibits NA+K+ATPase pump-disturbs the -Normal LDH &
cation gradient & loss of K+ & water- loss of membrane Haptoglobin
plasticity -Increased 2,3
BPG
Myeloperoxidase -Lack of Myeloperoxidase enzyme not yielding Hypochlorous -Increased candida infections Positive NBT
acid (bleach) in phagocytes unable to attack lipid membranes test/rhodamin
Deficiency of bacteria and kill it e positive

Pyruvate Carboxylase -Unable to make Oxaloacetate from Pyruvate which affects -Hypoglycemia -biotin &
the TCA cycle & gluconeogenesis, low ATP, decreased -Hyper ketosis aspartate
Deficiency glutamate, ow glucose -accumulation of acetyl Co-A in liver supplementatio
-Increased shunting to lactate- causes metabolic acidosis -hyperammonemia – low aspartate, malfunctioning urea cycle n
-Malfunctioning urea cycle- low aspartate
Essential Fructosuria -Fructokinase deficiency (unable to make F1P from Fructose) - -Excretion of fructose in urine
benign condition -Wrong diagnosis of Diabetes mellitus – Benedict's test
-Recurrent UTI’s & dehydration

Hereditary Fructose -Deficiency in Aldolase B (unable to convert F1P to -Nausea, vomiting, epigastric pain, hyperventilation (metabolic Avoid fructose
Glyceraldehyde & DHAP) acidosis) & symptoms of hypoglycemia in diet
Intolerance -Accumulation of F1P (phosphate trapping) -Long term: Hyperuricemia, signs of liver damage including
-symptoms begin when fructose is introduced into the diet hemorrhage, jaundice, hepatomegaly & hepatic failure.

Non-Classical -Deficiency of Galactokinase (GALK) (Unable to convert -Early onset of cataract in first few months of life
galactose to Galactose-1P)
Galactosemia -Begins w. consumption of Breast Milk
-Less severe (compared to classical type) - no metabolic
complications
Classical Galactosemia -Deficiency in Galactose 1-phosphate uridyltransferase (GALT) -Metabolic symptoms (vomiting, hypoglycemia)
(unable to convert Galactose 1-P to either UDP Galactose or -Eye: Formation of cataracts
Glucose 1-P) -Liver damage: Hemorrhage, jaundice & cirrhosis
-Accumulation of Galactose 1-P (which causes osmotic damage -Brain damage: Seizures, encephalopathy & mental retardation
& Phosphate trapping) (even after breast milk has been stopped)

Autosomal Dominant Cause Clinical Presentation Test Treatment

Achondroplasia -Mutation in the FGFR3 RTK-type receptor that makes it - Semi-dominance/Incomplete Dominance
constitutively active. -mature height <4 ft
-Inhibits production of Collagen II -Long bones are short
-Restricts chondrocyte proliferation which causes excessive (Most common type of dwarfism)
inhibition of bone growth (particularly of long bones)
Osteogenesis Imperfecta -Mutation in Type I collagen (the procollagen alpha (I) chain -Type I (mild): blue sclerae, bone fragility
genes. -Type II (perinatal lethal): blue sclerae, severe bone fragility, no
(Type I, II, III, IV) -Most clinically severe phenotypes from substitutions for an mineralization, skeletal deformity
invariant glycine. -Type III (deforming): blue-white sclerae, dentinogenesis
imperfect, bone fragility, short stature.
 -Substitutions closer to C-terminal are more detrimental due -Type IV (mild deforming): normal sclerae, dentinogenesis
to that collagen forms triple helix from C->N terminus. imperfecta, mild short stature, moderate skeletal fragility.

Familial -LDL-R (LDL receptor) mutation -Semi-dominance/Incomplete Dominance

-Class I: Defective synthesis – protein doesn't fold correctly -increased plasma cholesterol
Hypercholesterolemia -Class II: Defective transport from RER -increases synthesis LDL
-Class III: Defective Binding to transmembrane -Xanthoma (fatty deposits)
-Class IV: Defective clustering in vesicle -Corneal arcus
-Class V: Defective recycling of protein -Major risk for CHD, premature atherosclerosis
Marfan Syndrome -Fibrillin mutation causing weak elastic tissue -Heart: aortic root dilatation & dissection
-Eye: lens subluxation & retinal detachment
-Skeleton: tall & thin (long limbs & fingers –arachnodactyly)
Funnel chest (pectus excavatum)
Hereditary Spherocytosis -Nonfunctional skeletal membrane -Splenomegaly (only anemia with this) Blood smear
protein Spectrin, ankyrin, or Protein 4.1 -Jaundice
-the unstable membrane loses fragments -Gall stones (from hyperbilirubinemia)
-Usually, deficiency in spectrin
Emery-Dreifuss Muscular Mutation in Emerin or Lamin A/C -Contractures, especially in the elbows, ankles, neck (flexion
(Microscopy: fragile nuclei- chromatin spilling out of nuclear deformity of elbows, limited neck flexion)
Dystrophy envelope) -Muscle weakness & atrophy
-Conduction defects & arrhythmias
-Sudden heart failure
Dilated Cardiomyopathy Rare cause: Lamin A/C defect -Enlarged heart – Congestive heart failure
(Fragile nuclear lamina leading to damage of cellular contents
leading to cell death)
Lipodystrophy Lamin A/C defect – prelamin A interacts with an adipocytic TF - -Accumulation of adipose tissue in face & neck
-> impaired adipocyte differentiation -
(Can also be caused by infections)
Hutchinson-Gilford -Altered Lamin A which leads to unstable nuclear envelope, -Failure to thrive at 18-24 mo.
causes progressive cell damage (premature cell death) -prominent eyes, alopecia, aged looking skin, joint issues
Progeria -Sporadic -Life expectancy ~13 yrs (>80% deaths from MI or CHF)
Progressive External -POLG encoding DNA polymerase γ -Late age onset (18-40yrs)
-TWNK, encoding helicase Twinkle -Biochemical and histological muscle pathology (ragged-red muscle
Ophthalmoplegia (PEO) -Multiple genes involved (heterogeneity) fibers)

-Involves nuclear and mitochondrial genes (see mitochondrial for
more info)
(Most common inheritance Autosomal Dominant)
Epidermolysis Bullosa -Mutation in keratin 5 or 14
-Causes rupture of cells in the basal layer of the epidermis;
Simplex rupture of keratin IFs connecting down to basal lamina.
(3 types Dystrophic, Junctional, Simplex)
-Progressive muscle weakness & wasting (Bilateral Ptosis), exercise
intolerance.
-Male to male transmittance
-Fragile skin, minor mechanical friction/trauma
-Recurrent blister formation especially in hands and feet

Epidermolytic -Mutations in Keratins 1 & 10 -Red skin & blisters at birth

-Suprabasilar differentiation of keratinocytes, which weakens
Hyperkeratosis structural stability of keratinocytes
Ehlers-Danlos Syndrome -Defective fibrillar collagen synthesis or structure
-Type I: Mutation Collagen V (or I –rarer) -78%
(Type I, IV, VI, VII) -Type IV: Mutation in Collagen III –6%
-Type VI: Mutation in Lysyl Hydroxylase -2%
-Type VII: Defect in converting procollagen I into collagen I –3%
(>17 variants now recognized, many rare)
-Easy blistering
-Chronic wounding --> hyperproliferation & thickened scaly skin
-Type I: joint hypermobility, hyperextensive skin
-Type IV: vascular type: arterial, intestinal, uterine rupture, easy
bruising, thin translucent skin, varicose veins.
-Type VI: Ocular fragility: retinal hemorrhage & detachment,
corneal rupture. Kyphoscoliosis
-Type VII: Joint hypermobility
De vivo Disease -GLUT 1 deficiency--> low glucose in CSF/Brain-->Decreased -Refractory Infantile seizures Ketogenic Diets
ATP -Microcephaly & motor dysfunction
-Refractory infantile sei
Lactase Persistence -persistent lactase activity in population who domesticated -no symptoms when ingesting lactose
cows & consumed mil products into adulthood

X-Linked Recessive Cause Clinical Presentation Test Treatment

X-linked Cardioskeletal -X-linked disorder in cardiolipin synthesis – without cardiolipin -Cardiomyopathy
the inner membrane doesn’t function correctly (cristae do not -Generalized muscle weakness & Chronic fatigue
Myopathy with line up correctly) – causing Mitochondrial disruption & -Neutropenia
Neutropenia dysfunction (ETC doesn’t function) -Sperm cell defects
-High mortality in infancy – sudden infant death, infection, cardiac failure
(Barth Syndrome)
-
Hunter Syndrome -Deficiency of iduronate-2 sulfatase - like hurler syndrome but later presentation (2-4 yrs) & milder
-accumulation of dermatan sulphate & heparan sulphate course (survival into 30’s)
(Mucolipidosis II) -No corneal clouding
-Pearly papular skin lesions over scapulae & on lateral upper arms
& thighs
Chronic Granulomatous -Defect in NADPH oxidase complex (phagocyte oxidase) results -recurrent, life threatening bacterial & fungal infections & Negative NBT
in inability of phagocytes to destroy certain microbes (catalase granuloma formation test/abnormal
Disease positive) -most common organs involved- lung, skin, lymph nodes, & liver dihydro-
(NADPH Oxidase Deficiency) -Gp91phox mutations (70% cases) - heterogenous -Pneumonia, abscesses, suppurative adenitis, osteomyelitis, rhodamine test
(Similar to Myeloperoxidase deficiency) bacteremia/fungemia, superficial skin infections (cellulitis/impetigo)
Glucose 6-Phosphate -G6PD deficiency- causes decreased production of NADPH due -Decreased haptoglobin
to that it is not converting G6P to 6-phosphogluonoacetone -Increased LDH
Dehydrogenase (G6PD) -Inhibition of Glutathione peroxidase -Hemoglobinuria after a free radical insult
Deficiency -Hemolysis of RBCs due to increase in oxidants that attack the -Degmacytes / bite cells in peripheral smear
globin chains and produces Heinz bodies. -No splenomegaly
-Heinz bodies – intravascular hemolysis--> bite cells are then
removed by the spleen
(causes for oxidative stress: Infections, Drugs *sulpha drugs, anti-malarial, aspirin,
INH, Nitrofurantoin), Fava beans, certain chemicals)

X-Linked Dominant Cause Clinical Presentation Test Treatment

Adrenoleukodystrophy -Defective membrane protein that imports VLCFA into the -Onset 5-10yrs old
peroxisomes (defective breakdown of VLCFAs) - accumulation -Apathy, behavioral changes
(XALD) in brain (glial cells) and adrenal cortex -Spasticity, ataxia, visual loss
-Most common peroximal disorder -Death occurs a few years later
Charcot-Marie-Tooth -one form is caused by a mutation in Connexin 32 (in peripheral -Weakness & atrophy of distal muscles No-good
neurons) which are part of Gap junctions which seem to be -depressed or absent deep tendon reflexes treatments.
Disease (CMT) critical in supplying nutrients to the distant Schwann cells. -mild sensory loss Custom-made
-This causes demyelination & failure of peripheral neuron -Progressive degeneration of the muscles of the foot, lower leg, shoes & braces
function hand & forearm. can minimize
-Most common inherited peripheral neuropathy discomfort
Albort Syndrome -Mutation in α5 chain of Type IV Collagen (in basal lamina) -Nephritis
(Common inherited cause of kidney failure – X-linked -recessive -Deafness
& X-linked dominant) -Hematuria
-Proteinuria
-Hypertension
Pyruvate Dehydrogenase -deficiency Inability to convert Pyruvate to Acetyl Co-A -severe energy deficit impacts on brain development in utero -> Diet limited to
decreases. Shunted to Lactate Dehydrogenase – Lactic acid structural brain anomalies & epilepsy ketogenic
Complex Deficiency increases - Neurological defects (microcephaly, mental retardation) nutrients, high
 -Most common mutation (E1 subunit) in fat content &
-Deficient NADH leading to deficient ATP- predominantly rich in lysine,
affects the brain leucine

Mitochondrial Cause Clinical Presentation Test Treatment

LHON
Leber Hereditary Optic Neuropathy
NARP
Neurogenic Muscle Weakness, Ataxia
& Retinitis Pigmentosum
Mutation in Mitochondrial Protein-Coding gene: Subunits of -Progressive worsening of central vision
Complex I (NADH Dehydrogenase)- (mitochondrial gene) -blurred vision, loss of color distinction
(May be homoplasmic or heteroplasmic)
-Mutation in Mitochondrial Protein-Coding gene: ATPase 6 -Late-childhood or adult-onset peripheral neuropathy
gene of Complex V (ATP Synthase) -Ataxia, pigmentary retinopathy
(Always heteroplasmic)
(Less severe than leigh syndrome)

Leigh Syndrome -caused by mutation in mitochondrial protein-coding genes -Onset in 1st yrs, 50%die by age 3.
>75 genes-most are nuclear, but some are mitochondrial -progressive neurological, respiratory & cardiac degeneration
(genes involved in energy production) -Elevated lactic acid, hypotonia, spasticity, movement disorders, cerebellar ataxia, and
peripheral neuropathy.

MILS -Mutation in Mitochondrial Protein-Coding gene: ATPase 6 ^

gene of Complex V (ATP Synthase)
Maternally-Inherited Leigh (More severe due to greater degree of heteroplasmic)
Syndrome (a subtype of Leigh Syndrome)
MELAS - Mutation in Mitochondrial tRNA (Leucine) mutation -Stroke like episodes: vomiting, headaches, visual disturbances
(Always heteroplasmic) -Short stature
Mitochondrial Encephalopathy Lactic -Diabetes, sensorineural hearing loss
Acidosis & Stroke Like episodes -Encephalomyopathy
-Lactic Acidosis
MERRF Mutation in Mitochondrial tRNA (Lysine) mutation -Progressive myoclonic epilepsy & seisures
(Always heteroplasmic)
Myoclonus Epilepsy & Ragged Red
Fibers

Progressive External -mtDNA depletion or large deletions in mtDNA -Late age onset (18-40yrs)
-Multiple genes involved (heterogeneity) -Biochemical and histological muscle pathology (ragged-red muscle
Ophthalmoplegia (PEO) -Involves nuclear (see AD for more info) and mitochondrial genes fibers)
-Progressive muscle weakness & wasting (Bilateral Ptosis), exercise
intolerance.
-No male-to-male transmission
Kearns-Sayre Syndrome -Giant deletion in mtDNA in muscle (>80% ragged red fibers), -Progressive external ophthalmoplegia, retinopathy, cerebellar
not in blood ataxia, heart block
(KSS) (no Bone marrow involvement) -Reduced, variable life expectancy
-Heteoplasmic -Bilateral Ptosis
Pearson Syndrome -Giant deletion in mtDNA in all tissues with bone marrow -Pediatric disease
involvement -Pancytopenia (all tissues have mtDNA with deletions)
(More severe than KSS) -Sideroblastic anemia, exocrine pancreatic failure
-Death usually <4 yrs. - if survive, undergo phenotype switch to KSS
Other Cause Clinical Presentation Test Treatment
Acanthocytosis/Spur Cell -” spur cells” (acanthrocytes) -Very thin, older looking, jaundices -Blood smear
-if less deformable, spleen sequesters for destruction -Ascites
Anemia -This causes hemolytic anemia -Caput medusae, esophageal varices
-Usually caused by liver cirrhosis -Asterixis (liver flap)
-Reticulocyte count up,
-high plasma cholesterol
-high prothrombin time: risk for GI bleed
Botulism (clostridium -Caused by a toxin that is wither foodborne or in a wound. -Paralysis of respiratory & skeletal muscles
-The toxins cleave synaptobrevin (v-SNARE) -Flaccid Paralysis
botulism) -Vesicles carrying Acetylcholine can’t fuse & release NT at NMJ. -” Floppy baby syndromes”
-Constipation
-Loss of head control
-Hypotonia & Hyporeflexia
-respiratory difficulties
(Potentially fatal)
Tetanus (Clostridium -Retrograde axonal transport up into spinal cord & into cell of -Locked Jaw -Spatula test-
inhibitory interneuron -Prolonged contraction of skeletal muscles results in bite
tetani-neurotoxin) -Cleaves Synaptobrevin (v-SNARE) -Neck stiffness
-Prevents vesicle fusion & release of GABA & Glycine -Dysphagia
(inhibitory NTs) onto motor neuron of NMJ. -Pectoral & calf muscle rigidity
-Spasms
Gout -Increased function of Xanthine oxidase -Accumulation of Uric Acid in joints which causes swelling Allopurinol:
-large amounts of uric acid being produced from purines -Usually, patients have pain in their toes and fingers as well as other Xanthine
joints. Oxidase
inhibitor
Acquired Mitochondrial -AZT (Zidovudine) antiretroviral drug inhibits DNA polymerase -Myopathy in HIV patients
γ (the mtDNA pol) causes depletion of mtDNA. -Ragged red muscle fibers and crystallin inclusions –in histo
Myopathy in HIV patients (doesn’t inhibit DNA Pol δ-nuclear pol)
Alzheimer’s Disease Possible cause: -Progressive impairment of visual-spatial skill (gets lost), memory
Neurofibrillary tangles (intraneuronal) and β-amyloid/senile & cognition
plaques (extracellular) form from tau (MAP) malfunction which -Short term memory loss
Is hyperphosphorylated -Confusion, behavioral & psychotic symptoms, progressive memory
loss (last to go = deepest memories)
-Loss of bodily functions (incontinence, mute) & withdrawal
Epidermolytic -Mutation in keratin 9 -Redness or scaliness only expressed in palms & soles
(Many different types of Inheritance)
Plantopalmar
Keratoderma
Scurvy -Deficiency in Vitamin C -Bleeding gums, loosened/lost teeth, petechiae (pinpoint
hemorrhages around hair follicles, gums & nails), ecchymoses
-poor wound healing
-Joint & leg pains, poor bone development, anemia, tired, “weak
with an irritable melancholy & general fatigue
Diabetic Nephropathy -Hyperglycemia changes renal basement membranes (HSPGs) -Proteinuria
which change filter selectivity in kidney -fluid retention (edema)
-It causes GBM thickening, which increases collagen and -Hypertension
decreases HSPG, and causes expansion of the mesangial matrix. -Eventually renal failure
-These changes allow proteins and other molecules to cross -Most common cause of kidney failure in world
barrier
Arsenic Poisoning -usually from contaminated groundwater is the greatest -Dermatologic (rain drop melanosis, keratosis)
exposure risk -bladder cancer from drinking contaminated H2O
-Neurologic & cardiovascular toxicities, known carcinogen -Skin, lung, GI, liver, hematopoietic & lymphatic cancers
-Binds to PDH, α-ketoglutarate dehydrogenase, α-keto acid
dehydrogenase
Wet beri beri -Thiamine/B1 deficiency, normal function -Transketolase, -Lactic acidosis
oxidative decarboxylation -Congestive cardiac failure – high output cardiac failure
(Mostly caused by alcoholism in the US) -Arrhythmias
 -Affects heart & circulatory system -Peripheral edema
Dry beri beri -Thiamine/B1 deficiency- normal function -Transketolase, -Wernicke’s Encephalopathy (Ataxia, Confusion, Ophthalmoplegia)
oxidative decarboxylation -Kosakaoff Syndrome: (confabulation, Memory loss, Psychosis)
(Mostly caused by alcoholism in the US)
-damages nerves
Riboflavin/B2 Deficiency -Riboflavin/B2 Deficiency – normal function is for redox -Glossitis –Inflammation of tongue, magenta red color, fissures, atrophy of lingual
reactions papillae.
-Cheilosis - Fissures in lips.
-Angular stomatitis - Inflammation at conners of mouth
-Conjunctivitis
-Oral-ocular-genital syndrome Angular stomatitis, photophobia, scrotal dermatitis
-Anemia & Erythroid Hypoplasia - due to decreased activation of B6
Niacin/B3 Deficiency -Niacin/B3 deficiency – impaired function of NAD+ & NADP -Pellagra- 4D's – Diarrhea, Dementia, Dermatitis, Death
cofactors involved in oxidation reduction reactions -Casal’s necklace - Classic erythematous pigmented rash around
collar
Von Gierke Disease -G6Pase deficiency (only present in liver-ER) -Hepatomegaly
-Inability to release free glucose into blood, buildup G6P -Severe fasting hypoglycemia (Inhibition of glycogenolysis & gluconeogenesis)
(Type I GSD)
-Prevents glucagon regulation -Ketosis
(Glycogen structure normal) -Hyperlipidemia,
-Hyperuricemia (Severe gout)
-Lactic acidosis
-Hypertriglyceremia -epi -> release of FFA->TGs-> VLDL
Pompe Disease -Lysosomal α-1,4-glucosidase deficiency or Acid Maltase– -Cardiomegaly- death due to cardiac muscle, normal glucose levels
accumulation of lysosomal glycogen deposits in liver, heart, Infantile: Complete deficiency, first few months of life, Diaphragm
(Type II GSD)
muscle and heart
Adult: Partial deficiency, any age, proximal muscle deficiency
Cori Disease -Debranching enzyme (alpha1,6-glucosidase) deficiency, only -Mild Hypoglycemia
(Type III GSD) terminal glycogen branches used for blood sugar regulation: -Hepatomegaly that diminishes w. age
gluconeogenesis makes up the difference.
-Glycogen-dextrin like (due to short branches)
Anderson Disease -Branching enzyme deficiency, very long amylopectin chains -Cardiac or liver failure
cause liver to become cirrhotic (resembles autoimmune -Lethal within 2 years
(Type IV GSD)
response) -No hypoglycemia in the initial months

McArdle Syndrome -Muscle Glycogen Phosphorylase deficiency, affecting White -Muscle cramps, absent normal anaerobic production of lactate -Forearm
Muscle fibers (type II) (which use glycogen as source for during exercise exercise test
glucose for anaerobic glycolysis) -Abnormal amount of glycogen in muscle
(Glycogen is normal) -Myoglobin In urine
Her Disease -Liver glycogen phosphorylase deficiency causes glycogen -Hepatomegaly
storage -mild hypoglycemia
Autoimmune Diseases Cause Clinical Presentation Test Treatment
Bullous Pemphigoid -autoantibodies to hemisdesmosomal protein (which connects -Subepidermal blisters or Psoriasiform pattern
the basal surface epithelial cell and basement membrane) -Presents >60-yrs
-Disrupt dermal-epidermal junction -Itchy
Pemphigus Vulgaris -autoimmune disorder (or genetic defect) of desmosomal -blistering & raw sores on skin & mucus membranes (usually Steroid
cadherins (which normally resist shearing forces in epithelial appear in mouth first) Therapy
cell layers) -skin pulls apart --> abnormal movement of fluid within skin -->
(If untreated = fatal (systemic infection)) blisters
Goodpasture Syndrome -Auto-antibodies against Type IV collagen (α3 chain) -Onset: teens-20's. Mostly in males
-Hemoptysis
-Inflammatory destruction of BM in kidney glomerulus & lung -Glomerulonephritis with progressive renal failure
alveoli