Disorders of Metabolism Flashcards
Pyruvate dehydrogenase complex (PDH) deficiency
X-linked; buildup of pyruvate shunted to lactate and alanine;
neurologic defects, lactic acidosis, increased serum alanine starting in infancy
Electron Transport Chain inhibitors (blocks ATP synthesis) & Uncoupling agents (produce heat)
Complex I: Rotenone Complex III: Antimycin A Complex IV: Cyanide, CO, Azide ATP synthase (Complex V): Oligomycin Uncoupling agents: 2,4-dinitrophenol, aspirin, thermogenin
G6PD deficiency
decreased NADPH in RBCs; most common human enzyme def.
hemolytic anemia, Heinz bodies (denatured Hb), Bite cells
Essential fructosuria
defect in fructokinase;
benign, fructose in blood and urine
Fructose intolerance
deficiency in aldolase B;
Fructose-1-P accumulates which inhibits gycogenolysis and gluconeogenesis;
hypoglycemia, jaundice, cirrhosis, vomiting
Galactokinase deficiency
deficiency in galactokinase, galactitol accumulates;
galactose in blood and urine, infantile cataracts, failure to track objects or develop social smile
Classic galactosemia
absence of galactose-1-P uridyltransferase;
failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, can lead to E. coli sepsis in neonates
Lactase deficiency
stool has decreased pH and breath has increased Hydrogen w/ lactose tolerance test; normal mucosa in pts with hereditary lactose intolerance
essential glucogenic amino acids
Met, Val, His
essential glucogenic/ketogenic amino acids
Ile, Phe, Thr, Trp
essential ketogenic amino acids
Leu, Lys
acidic amino acids
neg charge;
Aspartate, Glutamate
basic amino acids
Arg, Lys, His
amino acids for growth
Arg, His
amino acids in histones
Arg, Lys
N-acetylgutamate deficiency
required cofactor for Carbamoyl phosphate synthetase I (Urea cycle);
leads to hyperammonemia;
in neonates: poorly regulated respiration and body temp, poor feeding, developmental delay, intellectual disability (identical presentation as in carbamoyl phosphate synthetase I def.)
Ornithine transcarbamylase deficiency (OTC)
most common urea cycle disorder (only X-linked urea cycle disorder, others are AR);
excess carbamoyl phosphate converted to orotic acid;
increased orotic acid in blood and urine, decreased BUN, sx of hyperammonemia, NO megaloblastic anemia (vs. orotic aciduria);
infant is lethargic, poorly feeding, poorly controlled breathing and body temp
PKU
disorder of aromatic amino acid metabolism leads to musty body odor;
screening occurs 2-3 days after birth (normal at birth b/c of maternal enzyme during fetal life)
Maple syrup urine disease
decreased alpha-ketoacid dehydrogenase (B1) causes incrased alpha ketoacids in blood, blocks degradation of Isoleucine, Leucine, Valine;
CNS defects, intellectual disability, death
Alkaptonuria (ochronosis)
deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate leading accumulation of homogentisic acid in tissue;
dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air, may have debilitating arthralgias
Homocystinuria
d/t: 1) Cystathionine synthase def. 2) decreased affinity of cystathionine synthase for pyridoxal phosphate (B6) 3) Homocysteine methyltransferase (methionine synthase) def.;
increased homocysteine in urine, intellectual disability, osteoporosis, MARFANOID HABITUS, kyphosis, len subluxation (downward and inward), thrombosis, atherosclerosis
Cystinuria
defect of renal PCT and intestinal amino acid transporter preventing reabsorption of Cysteine, Ornithine, Lysine, Arginine (COLA);
urinary cyanide-nitroprusside test is diagnostic
Von Gierke disease (Type I)
Glucose-6-phosphatase def.
Pompe disease (Type II)
Lysosomal alpha-1,4-glucosidase (acid maltase) def.
Cori disease (Type III)
Debranching enzyme (alpha-1,6-glucosidase) def.
McArdle disease (Type V)
skeletal muscle Glycogen phosphorylase (myophosphorylase) def.
Andersen’s disease (Type IV)
Glycogen debranching enzyme def.
Hers disease (Type VI)
hepatic Glycogen phosphorylase def.
Fabry disease
alpha-galactosidase A def.;
Ceramide trihexoside accumulates
Gaucher disease
Glucocerebrosidase def.;
glucocerebroside accumulates
Niemann-Pick disease
sphingomyelinase def.;
sphingomyelin accumulates
Tay Sachs disease
Hexosaminidase A def.;
GM2 ganglioside accumulates
Krabbe disease
Galactocerebrosidase def.;
Galactocerebroside, psychosine accumulate
Metachromatic leukodystrophy
Arylsulfatase A def.;
Cerebroside sulfate accumulates
Hurler syndrome
alpha-L-iduronidase def.;
Heparan sulfate, dermatan sulfate accumulate
Hunter syndrome
Iduronate sulfatase def.;
Heparan sulfate, dermatan sulfate accumulate
Systemic Primary Carnitine deficiency
defect in tranport of LCFAs into mitochondria leads to toxic accumulation;
weakness, hypotonia, hypoketotic hypoglycemia
Medium chain acyl-CoA dehydrogenase deficiency
decreased break down of FAs into acetyl-CoA leads to accumulation of 8-10 carbon fatty acyl carnitines in blood and hypoketotic hypoglycemia;
may present in infancy or early childhood w/ vomiting, lethargy, seizures, coma, liver dysfunction
Hyperchylomicronemia (Type 1)
LPL def. or altered apolipoprotein C-II;
elevated Chylomicrons, TG, Cholesterol
Familial Hypercholesterolemia (Type IIa)
absent or defective LDL receptors;
elevated LDL, cholesterol
Hypertriglyceridemia (Type IV)
hepatic overproduction of VLDL;
elevated VLDL, TG
Abetalipoproteinemia
decreased synthesis of apolipoprotein B leads to inability to generate chylomicrons, decreased cholesterol and VLDL secretion into blood thus fat accumulates in enterocytes
