shosh: diseases in biochem

• Most common glycolytic enzyme deficiency
• Causes hemolytic anemia, since inability to maintain Na/K pump leads to RBC swelling and lysis

• Inability to synthesize acetyl CoA from pyruvate and alanine causes buildup of substrates, and lactic acidosis
• Seen in alcoholics, due to B1 (thiamine) deficiency
• Neurological deficits

• Hemolytic anemia, due to oxidative stress (antimalarials, sulfonamides, infection)
• X-linked
• Oxidized Hb precipitates in RBCs, and forms Heinz bodies
• Bite cells on peripheral smear

• Aldolase B deficiency
• Accumulation of fructose-1P inhibits glycogenolysis and gluconeogenesis
• Symptoms include hypoglycemia, jaundice, cirrhosis, and vomiting
• Appears in babies, when they start eating fructose

• Fructokinase deficiency
• Fructose appears in blood and urine
• Benign

• Galactose 1P uridyltransferase deficiency
• Toxins accumulate in eye and neurons
• Symptoms include failure to thrive, jaundice, hepatomegaly, infantile cataracts, and retardation

• Most common defect in the urea cycle
• X-linked
• Excess carbamoyl phosphate is converted into orotic acid, which builds up in the blood and urine
• Decreased BUN
• Ammonia intoxication

• Phenylalanine hydroxylase or tetrahydrobiopterin deficiency
• Phenylalanine cannot be converted into tyrosine, making tyrosine and essential AA
• Presents with mental retardation, growth retardation, seizures, albinism (lack of melanin), eczema, and a musty body odor

• Homogentisic acid oxidase deficiency causes impaired tyrosine degradation
• Findings include dark CT, pigmented sclera, urine that blackens in the air
• Arthralgias

Aldose reductase converts glucose to sorbitol, which accumulates in cells and causes osmotic damage (re: cataracts, retinopathy, peripheral neuropathy, seen in diabetes)

Can be due to a tyrosinase deficiency (tyrosine is converted to melanin) or a failure of neural crest cells to migrate

• Can be due to a deficiency in B6, B12, or folate
• Can be due to a mutation in cystathione synthase or homocysteine methyltransferase
• Causes mental retardation, osteoporosis, kyphosis, lens subluxation, and atherosclerosis

• B12 is needed to activate folate and to convert methylmalonyl CoA to succinyl CoA
• Lack of active folate causes megaloblastic anemia
• Buildup of methylmalonyl CoA causes peripheral neuropathy

• Caused by an AR defect in the renal cysteine transporter
• Cystine buildup precipitates as stones
• Treat with acetazolamide to alkalinize urine (since cystine is more soluble at high pH)

• Due to a defect in branched amino acid dehydrogenase
• Buildup of isoleucine, leucine, and valine
• Severe CNS defects and death

• Defective tryptophan reabsorption in urine
• Causes pellagra like symptoms (diarrhea, dermatitis, dementia), since tryptophan is used to make niacin

• Deficient glucose 6 phosphatase
• Severe fasting hypoglycemia and hepatomegaly
• Doll-like facies
• Hyperlipidemia
• Increased blood lactate

• Deficient lysosomal a-1,4 glucosidase
• Cardiomegaly

• Deficient debranching enzyme
• Glycogen looks abnormal under a microscope, but little or no hypoglycemia

• Deficient glycogen phosphorylase in skeletal muscle
• Cramps and myoglobinuria after exercise

• Deficient glycogen phosphorylase in the liver
• Hepatomegaly
• Mild hypoglycemia (gluconeogenesis is intact)

• Deficient a-galactosidase A
• XR
• Peripheral neuropathy
• Angiokeratomas
• Cardiovascular and renal disease

• Deficient B-glucocerebrosidase
• Hepatosplenomegaly
• Aseptic necrosis of head of femur
• Crumpled tissue paper macrophages

• Deficient sphingomyelinase
• Progressive neurodegeneration
• Hepatosplenomegaly
• Cherry-red spot on macula
• Foam cells

• Deficient hexosaminidase A
• Progressive neurodegeneration
• Cherry-red spot on macula
• NO hepatomegaly

• Deficient galactocerebrosidase
• Peripheral neuropathy
• Optic atrophy
• Globoid cells

• Deficient arylsulfatase A
• Central and peripheral demyelination, with ataxia and dementia

• Deficient a-L-iduronidase
• Gargoylism
• Airway obstruction
• Corneal clouding
• Hepatosplenomegaly
• (Hunter's syndrome is like Hurler's, but more mild, and XR, with no corneal clouding)

• Inability of enterocytes to form chylomicrons
• Decreased TGs, cholesterol, and FAs
• Acanthocytes
• Steatorrhea
• Night blindness

• Defective lipoprotein lipase or ApoC-II (activates LPL
• Pancreatitis, hepatosplenomegaly, xanthomas
• NO increased risk for atherosclerosis

• Deficient LDL receptors
• AD
• Accelerated atherosclerosis (homozygotes die of heart failure by 20)
• Corneal arcus

• Hepatic overproduction of VLDLs
• Pancreatitis