Disease Cause Clinical Presentation Test Treatment Memory Aid Other Notes

Fatty Acid/Ketone Diseases - MCB

Primary Carnitine Deficiency
-Defect in plasma membrane Carnitine
transporter --> poor uptake of Carnitine
by muscle
-Carnitine lost in urine
-Poor uptake of fatty acids for oxidation Hypoketotic Hypoglycemia
(↓Ketogenesis, ↓β-Oxidation, -Dilated Cardiomyopathy
↓Glucogenesis) -Encephalopathy
Carnitine Deficiency -Muscle Weakenes (myopathy,
myoglobinuria)
Secondary Carnitine Deficiency -Hypotonia
-Patients w. liver & Kidney disease
-Malnutrition & strict vegetarians
-Increased demand in Pregnancy
-Hemodyalysis Patients - removes
Carnitine
↑Free Carnitine, ↑FFAs/FA-CoA Hypoketotic Hypoglycemia
-Inhibition of FA oxidation & (during periods of extended
CPT-1 Deficiency
glucogenesis fasting, hepatic dysfunction)
(Carnitine Acyltransferase-1/CAT- -Hepatic Form- MC -Adrenergic Symptoms
1) -Neuroglycopenic Sympstoms
-Weakeness
Slow twitch muscle fibers affected Myalgia & tenderness Liver
CPT-2 Deficiency -↑ in Lactate -Exercise intolerance occurs
(Carnitine Acyltransferase-2/CAT- -No second wind phenomenon after prolonged exercise &
- Accumulation of neutral lipid in muscle worse during fasting
2) -Acyl Carnitines in Urine
Muscle Glycogen Phosphorylase Exercise intolerance/cramps Forearm exercise McArdle=Muscle
deficiency after strenous brief exercise test Type V -Glycogen
-Fast twitch White Muscle fibers (type II) -Second wind phenomenon seen storage disease
affected (which use glycogen as source -Myoglobin In urine
McArdle Syndrome for glucose for anaerobic glycolysis) -Arrhythmia from electrolite
-Normal Lactate levels disbalance
-Abnormal amount of glycogen in
muscle
(Blood Glucose levels usually unaffected)
Most common inborn error of FA Adrenergic Symptoms Avoid fasting
oxidation Neuroglycopenic Symptoms
-Leading cause of SIDS (Sudden Infant (Due to Hypoglycemia)
Death Syndrome) -Metabolic Acidosis (Nausea,
-Infants dependent on Breast Milt-which vomiting, acute abdominal pain)
contains Medium Chain FAs -Aspiration - high chances in Crib
-↑ dicarboxylic acids-> Metabolic -↑Acyl Carnites in Urine
Medium Chain Acyl-CoA acidosis -Liver dysfunction
Dehydrogenase Deficiency -↓ATP->↓Gluconeogenesis -> -Hyperammonemia
(MCAD) Hypoglycemia -Seizures
-↓Acetyl CoA production-> ↓Ketone -Coma
production-> Hypoketosis. & ↓NAG,
↓Urea cycle --> Hyperammonemia
-Fasting--> Hypoglycemia--> ↓β-
Oxidation
-Infections trigger MCAD
 PEX gene mutations (12 diff. genes)
-Peroxisomal abiogenesis, failure to
import peroximal proteins
-Accumulation of Very Long Chain
VLCFA & Branched Chained Fas
-↓Synthesis of PAF (plasmologen)
-Cerebrohepatorenal Syndrome
Zellweger Syndrome -Lack of bile acids->↓Fat absorption->
↓ATP
ABCD 1 gene mutation -
Adrenoleukodystrophy protein (ALDP)
Defect in transport of VLCFA into
X-linked peroxisomes
-Demyelination in Brain- Accumulation
Adrenoleukodystrophy
in brain (glial cells) and adrenal cortex
(XALD) -Most common peroximal disorder
Craniofacial Dysmorphisim (high Autosomal Recessive
forehead, hypoplastic Skeletal Muscle
supraorbital ridges, epicanthal
folds, midface hypoplasia, large
fontanel)
-CNS Hypomyelination->
Neuronal Migration Defects
-Hepatomegaly
-Renal Cysts
-Decreased fat absorption (lack of
bile acids)
-Muscle weakness (lack of
plasmalogen)
-Seizures
Onset 5-10yrs old X-Linked Recessive
-Apathy, behavioral changes
-Spasticity, ataxia, visual loss
-Adrenal Insufficiency (weakness,
weight loss, skin changes,
vomiting, coma)
-Sexual Dysfunction (Damage to
interstitial cells of Leydig)
-Death occurs a few years later

PHYH gene & PEX7 gene mutation Refsum = bRanched

-Deficiency in Phytanoyl-CoA Progressive muscle weakness
Hydroxylase --> ɑ-Oxidation defect -Peripheral polyneuropathy
-Accumulation of Phytanic Acid (plant -Cerebellar ataxia
chlorophyll, beef & dairy products) -Ichthyosis
Adult Refsum Disease -Incorporation of branched chain FAs in -Retinitis Pigmentosa
the membrane lipids-> ↑fluidity of the -Anosmia diet, plasmapheresis
neuronal membranes -> affects nerve -Scaly skin
conduction -Ataxia
(Neurocutaneous Syndrome) -Cataracts/Night blindness
PEX 1 or PEX6 (ATPase requred for -Shortening of the 4th toe
-Epyphisial Dysplasia
Infantile Refsum Disease peroxisoal protein import)
-Part of Zellweger Spectrum
1.Von Gierke Disease- Glycogen utilization defect
2.Hederitary Fructose Intolerance -Aldolase B Def.
Hypoglycemia &
3.Classical Galactosemia - Galactose utilization defect
Hyperkeratosis 4.Alcoholism
(↓Glu & ↑Ketones) 5.Pyruvate Carboxylase Def. - ↓OOA, ↓Gluconeogenesis

1.Carnitine Def.
Hypoglycemia & Hypoketosis 2. Medium Chain Acyl-CoA Dehydrogenase Def.
3. CPT-1 Def.
(↓Glu & ↓Ketones)
4. Carnitine Translocase Def.
↓Insulin: Glucagon ratio Hyperglycimia >200 mg/dl
-Insulin no longer inhibiting ketogenesis -Dehydration-glucosuria,
-↑FA oxidation ketonuria
-Acetyl-CoA present exceeds the ox. -Nausea & Vomiting
Capacity of liver -Abdominal Pain
-Mainly DM Type I -Kussmaul Breathing (deep
Diabetic Ketoacidosis
-High anion gap Metabolic acidosis (pH breathing)
<7.2) due to ketone bodies -Fruity odor (acetone)
-↓Bicarb (<15mEq/L) used for -Hyperglycemia - Glucosuria w.
neutralizing the blood water loss
-Hypotension & Coma
 Sphingolipidoses/Lysosomal Diseases - MCB
Sphingomyelinase Deficiency Type A: Severe - onset in infancy, Histo:
-Sphinogmyelin accumulates in death in early childhood -Foamy
lysosomes (in CNS, Liver, Spleen, Type B: Milder- onset in mid Macrophages w.
Macrophages) childhood, survival into numerous lipid-
-1:250,000 more common in Ashkenazi adulthood filled vacuoles
Jews -Hepatosplenomegaly -Zebra bodies
Niemann-Pick Disease -Failure to thrive (myelin-like
-Progressive loss of psychomotor lysosomal
function inclusion bodies in
-Interstital Lung Dx-> recurring EM)
inf.
-Cherry Red Spot in retina

HEXA mutation - ɑ subunit deficiency

-Hexosaminidase A deficiency
-Accumulation of GM2 Gangliosides in
Tay-Sachs Disease Lysosomes (mainly in Neurons) Progressive psychomotor
-General Population 1:300 deterioration
Histo:
-Ashkenazi Jews 1:30 -Ataxia, Developmental
-Onion Skin
regression, severe intellectual
Lysosomes in EM
HEXB mutation - β subunit deficiency disability
-Vacuolated
-Haxosaminidase A & B deficiency -Cherry Red Spot in retina
Lymphocytes
-GM2 Gangliosides & Globosides -Blindness
-Ballooned
Sandhoff Disease accumulate -Exaggerated startle response
Neurons
(faster progression than ^) -Death by age 2-3
(NO Hepatosplenomegaly)

GM2A Mutation -Activator Deficiancy

GM2 Activator Deficiency -GM2 Gangliosides accumulate
Glucocerebrosidase Deficiency (cleaves Type 1: Nonneuropathic (mild) Histo: Gauch my BONES
glucose from glucocerebrosides) -Bone pain, osteoporosis, -Gaucher cells hurt, Bro
-Glucocerebrosides accumulate in frequent fractures (crumpled paper (GlucocereBrosid
Macrophages & other phagocytic cells -Hepatosplenomegaly cytoplasm es)
(mainly in Liver, Spleen, Bone Marrow) -Anemia appearance)
-General Population 1:70,000 -Thrombocytopenia/
-Ashkenazi Jews 1:855 pancytopenia
-Nose bleeds, deficient clotting
Type 2: Acute Infantile
Neuropathic
-Onset by 3 mo - Death by 2yo
Gaucher's Disease -Extensive brain damage
Type 3: Chronic Neuropathic
-Slower progression, neural
damge, seizures, ↓cognition
Parinatal Lethal Form
-Severe neural damge, fluid acc.
(cherry red spot can occur, but
not common)
 X-linked semi-dominant Burning extremity pain (limited Histo: (GlucocereBrosides)
-ɑ-galactosidase deficiency (cleaves blood supply to nerves) -Zebra bodies in
terminal galctose of Gb3) -Renal Failure kidneys
-Gb3 acc. Mainly in endothelium of -Cardiovascular Disease Urinalysis:
blood vessels -Angiokeratomas (red/blue -Maltese Crosses in
Fabry's Disease papules on the skin) Urine (diffraction
-NO Organomegaly of lipid bodies in
polarized light)

Deficiency of Arylsulfatase Demyelination of CNS Histo:

-Acc. of Sulfatides -Irratibility -Acc. of
-Feeding diffculties multinucleated
-Muscle spasms globoid cells in
Metachomatic Leukodystrophy -Poor head control CNS
-NO Organomegaly
Deficiency of β-galactosidase Demyelination of CNS & PNS Histo:
-Acc. of Galactocerebrosides & -Peripheral neuropathy, ataxia, -Metachromatic
psychosine (neuro-toxin) difficulty speaking & walking, Granules in cells
Krabbe's Disease memory loss -Swollen neurons
(Globoid Cell Leukodystrophy) -Gallbladder polyps
-Risk of Cancer
-NO Organomegaly

Hypercholestorelemia
Smith-Lemli-Opitz Syndrome
(SLOS)
Elevated Plasma Cholesterol
-Major Public Health problem, 34 m.
Americans
-↑ risk for atherosclerosis & CHD
(only a weak correclatiion between
dietary & plasma cholesterol)
Mutation in DHCR7 gene
-Deficiency in 7-Dehydrovholesterol
reductase
(the final step in Cholesterol synthesis)
-Cholesterol precursors acc. In the cells
-Cholesterol is necessary for embryonic
development, including Shh signaling
Cholesterol - MCB
Xanthoma- cholesterol depisits
under the skin, often at joints &
tendons
Xanthelasma-smaller cholesterol
deposits often around eyelids
Congenital abnormalities
(Microcephaly, distinctive facies,
Malformation of the heart, lungs,
kidneys, GI tract, & genitalia)
-Syndactyly
-Intellectual disability
-Learning/Behavioral Problems

Cholesterol is released from the liver to Risk factors

the bile (5F’s): female,
-Solubilized by bile salts & phospholipids fat(obesity),
-There must be an adequate ratio of bile fertile
Cholelithiasis salts, phospholipids otherwise (multiparity),
(Cholesterol Gallstone Disease) cholesterol will precipitate to gall stones forty, fair.
-↓Bile salts/Phospholipids
-↑Cholesterol

Dislepidimias - MCB
Lipoprotein Lipase/LPL (In Blood Vessels - Eruptive Xanthoma in Buttocks ↑Chylomycrons in Autosomal Recessive
degrades TAG in Chylomycrons & VLDLs) -Acute Pancreatitis (Severe Fasting Blood:
ApoC-II Deficiency (Potent activator of epigastric pain) origin band-
LPL -Lipemia Retinalis (Opalescent, Creamy floating
Hyperchylomicronemia -No link to CVD creamy retinal blood vessels) layer
-Hepatosplenomegaly -TG: Very High
(Type I Hyperlipoprotenemia) -Fatty Liver/Hepatic Steatosis -LDL & HDL: Low
-Childhood Onset (learn to avoid
fat consumption)

Familial Hyperlipoproteinemia
(Type IIA)
LDL Receptor (loss of function) - most Outward physical manifestations Plasma LDL: Very Mipomersen- Apolipoprotein B Autosomal Dominant
common are limited High anti-sense oligonucleotide, (semi)
ApoB-100 (loss of function) -Xanthomas (tendonous) -Plasma ↓VLDL synthesis
PCSK9 (gain of function) -Xanthelasma Cholesterol: Very Lomitapide- Inhibits
-LDL Particles are not cleared from the -Premature Atherosclerotic CVD High Microsomal TAG Transfer
blood Protein (MTP), Inhibits
-Heterozygotes: CAD by 45, LDL-plasma formation of Chylomycrons &
2-3X normal VLDL
-Homozygotes: CAD in childhood, Death
by 30, Plasma LDL many fold higher

Familial (Primary) - ApoB-100 (gain of Xanthoma Elevated LDL & ⭐ Q!

Hyperlipoproteinemia
(Type IIB/Combined
Hyperlipoprotenemia)
function-AD) -Xanthelasma VLDL
-Aquired (Secondary) - Common in -Corneal Arcus -Cholesterol High
Metabolic Syndrome -Aspects of metabolic syndrome -TG High-Very High
-Premature atherosclerotic CVD -HDL-Low
 ApoE (ε2) - in IDL's & Chylomycron Xanthomas Elevated IDL & Autosomal Recessive
Dysbetalipoproteinemia/ Broad remnants -Palmar Xanthomas Chylomycron
-Tuberoeruptive Xanthoma remnants
Beta Disease -Premature atherosclerotic CVD -Cholesterol High
(Type III Hyperlipoproteinemia) -TG Very High

Uknown etiology Xanthonas (variable) Elevated VLDL

Familial Hypertriglyceridemia/
Pre-Beta hyperlipoprotenemia
(Type IV Hyperlipoprotenemia)
-Heterogenous -Acute Pancreatitis -TG Very High
-Greater production of VLDL by liver & -↑Risk of atherosclerotic CVD -Cholesterol High
Lower activity of LPL (not as great as Type IIA & IIB) -HDL: Low to
normal

Mixed Hyperlipoproteinemia
Combined Hyperchylomicroneia
Hyperprebetalipoproteinemia
(Type V Hyperlipoproteinemia)
ApoA-V (Loss of function)- activates LPL Xanthoma Elevated VLDL & Autosomal Recessive
(similar to ApoC-II) -Lipemia retinalis Chylomycrons
-High Carb diet can shift Type I to Type V -Abdominal Pain/pancreatitis -Cholesterol -
Aquired: Common in Metabolic -Low to moderate ↑risk of Normal to High
Syndrome Coronary Heart Disease -TG Very High
-HDL Very Low

Microsomal Triglyceride Transfer Fat Malabsorption Chylomicrons, ⭐ Q!

Protein (MTP) - Packs the TG's & C
-Impared production of Chylomicrons &
VLDL
Abetalipoproteinemia
-Onset in infancy, failure to thrive VLDL, LDL Very Autosomal Recessive
-Death in Childhood is common Low
-Steatorrhea (fatty stools, -ApoB-100 &
malodorous (Floaty stools) ApoB48: Low
-Fatty Lover -TG & C: Low
-Deficiency of Essential Fas
-Fat Soluble Vitamin Deficiencies
-Vita A: Retinitis Pigmentosa,
Night blindness
-Vit D: Rickets, Osteomalacia
-Vit E: Spinocerebellar
Degeneration, Acanthocytosis
-Vit K: Blood Clotting

Lecithin Cholesterol Acyltransferase Partial LCAT Deficiency

(LCAT)-turns Cholesterol. into
Cholesterol Esters For incorporation
into HDL
-Impaired formation of HDL
LCAT Deficiency -ApoA-1 Degraded
-Free cholesterol accumulated in other
lipoproteins & tissues
-Fish- Disease - Progressive
corneal opacification due to
cholestterol accumulation
Complete LCAT Deficiency
-Progressive corneal opacification
-Hemolytic Anemia
-Kidney Failure
-Modest ↑ in CVD risk

ABCA1 Deficiency (Synthesis of HDL) Enlarged Orange Tonsils TANG! I can say
-Free cholesterol accumulates in -Foam Cells my ABC's
peripheral tissue (reticuloendothelial -Hepatosplenomegaly (Tang is also
cells (Macrophages) -Increased CVD Risk orange-orange
tonsils)
Tangier Disease
 Hypercholesterolemia Drugs/Treatments
Statins HMG-CoA reductase Inhibitor
Cholestyramine Bile Acid Sequestrans
Ezetimibe Inhibitors of Cholesterol absorpiton
PCSK9 Inhibitors Inhibits break down of LDL receptor
Nicotinic Acid (Niacin, B3) Questionable efficacy…
LDL Apheresis Physical removal of LDL from plasma
Liver Transplantation Provides LDL receptor