Amino Acids
Deficiency in branched chain alpha-ketoacid dehydrogenase complex which results in elevations of branched-chain amino acids (BCAA's) in plasma, and alpha-ketoacids in the urine.
Symptoms: Low muscle tone, fussiness, and inability to wake up.
Treatments centers on a diet low in isoleucine, leuicine, and valine.
Maple Syrup Urine Disease
2nd most common cause of hemolytic anemia, resulting in a presence of echinocytes and elevated levels of 2,3-BPG.
Pyruvate Kinase Deficiency
Mutations in the genes that make up the PDH complex which results in increased amount of pyruvate being converted to lactate.
Pyruvate Dehydrogenase Deficiency
Deficiency in medium chain acyl-coA dehydrogenase
Symptoms: vomiting, lethargy, frequent coma after napping
Lab values: Hypoglycemia, increase in medium acylcarnitines, increase in medium chain dicarboxylic acids in the urine, decrease urinary ketones
MCAD
B-hexosamidinase A deficiency causing nearby nervous system cells to lose function.
Accumulation of GM2 ganglioside, which is toxic and leads to disease pathology.
Symptoms: Improper neuronal activity, cell death. In infants there is regression; loss of motor skills like turning over, sitting, crawling, and are startled easily. Eye abnormality called cherry red-spot
Tay-Sach's Disease
Deficiency in phenylalaline hydroxylase.
Results in accumulated levels of phenylalaline.
Symptoms: Excess phenylalanine will cause intellectual delay, seizures, and tremors early in life. And because melanin is derived from tyrosine, patients with PKU will have subsequent low levels of melanin, resulting in pale skin, fair hair, and blue eyes.
Phenylketournia (PKU)
Excess lactate released by cells during glycolysis leading to dangerously low blood pH, which results in poor oxygen transport and LDH dysfunction/other metabolic conditions
Lactic Acidosis
Deficiency in the enzyme that converts pyruvate to oxalocetate, resulting in an accumulation of lactic acid in the blood, seizures, muscle weakness (hypotonia), and uncontrolled movement (ataxia).
Pyruvate Carboxylase Deficiency
Results in impaired utilization of long chain fatty acids for energy production.
Symptoms: hypoglycemia, hypoketotic, enlarged liver, liver malfunction,
Lab values: increased carnitine
CPT-1 Deficiency
Deficiency in Glucocerebrosidase (or acid beta-glucosidase) leading to an accumulation of glucocerebroside.
Symptoms: Hepatopsplenomegaly, pancytopenia mental retardation in infantile form, long bone degeneration.
Gaucher's Disease
Prion diseases that are believed to cause neurodegenerative disease by acting like a template to misfold.
*There are two!
Mad Cow Disease inherited through infection
Creutzfeldt-Jakob Disease (CJD) inherited mutations
Mutation of enzyme responsible for the last step of the oxidative phase of PPP that results in hemolytic anemia.
Erythrocytes are unable to produce NADPH, so they are not protected from oxidative stress.
Oxidative stresses include: Oxidizing medication (sulfa), oxidizing foods (fava beans), and infection
G6PDD
Inhibits aconitase in TCA
Fluorocitrate (rat poison)
Impaired perioxisome biogenesis leading to an abscence of perioxisomes and accumulation of VLFAC's.
Symptoms: Feeding difficulty, failure to gain weight, hypotonia, facial features similar to Down syndrome, respiratory distress, GI bleed, liver failure
Zellweger Syndrome
Mutations in mitochondrial tRNA genes
Symptoms: Encephalopathy (seizures, dementia), recurrent stroke like episodes at a young age, myopathy, and lactic acidosis; ataxia, deafness, pigmentary retionpathy, and short stature
MELAS (mitchondrial myopathy, encephalopathy, lactic acidosis, and stroke)
Vitamin C Deficiency
Decreased tensile strength of collagen
Scurvy
*Belongs in amino acid category but there was no room*
Abnormal protein causing this disease is beta-amyloid
Alzheimer's disease
Inhibits lipoic acid formation, which is a cofactor for Alpha-ketoglutarate Dehydrogenase
Arsenite
(Arsenic Poisoning)
Defect in alpha-oxidation of phytanic acid. Leads to large accumulation of phytanic acid in the blood and tissues.
Symptoms: shortening of the 4th toe, motor/sensory neuropathy
Prevention: Restrict dietary intake of dairy and meat products
Refsum's disease
mtDNA mutation, specifically a defect in NADH dehydrogenase (Complex I)
Symptoms: Begins with blurring and clouding of vision, progresses to severe loss of sharpness and color
LHON: Leber Hereditary optic neuropathy
Genetic defects of fibril-forming collagen, or the availability of copper.
Ehlers-Danlos Syndrome
*Belongs in amino acid category but there was no room*
Abnormal protein causing this disease is Beta-Globin
Sickle Cell Anemia
HbS: Glu-->Val
HbC: Glu-->Lys
HbSC: Glu-->Val and Glu-->Lys
B1 (thamine) deficiency in alcoholics, resulting in a triad of ataxia, confusion, and ophthalmoplegia
*Not enough room in other category*
An uncoupler that binds to ATP Synthase and blocks the flow of protons through the channel, which causes the rotation and ATP synthesis to cease
Oligomycin
Mutations in both nuclear and mitochondrial genes! Includes components in complex 1, 2, 3, 4, 5, and PDH.
Leigh Syndrome