Metabolic Disorder Defective Molecule Flashcards
I-Cell Disease
N-acetylglucosaminyl-1-phosphotransferase
failure of Golgi to phosphorylate mannose residues
G6PD Deficiency
Glucose-6-Phosphate Dehydrogenase
(necessary for HMP shunt and reduction of Glutathione, which is important for detoxifying free radicals and peroxides–> leads to hemolytic anemia)
Essential Fructosuria
Fructokinase
Fructose Intolerance
Aldolase B
–> leads to accumulation of Fructose-1-Phosphate (hypoglycemia, jaundice, cirrhosis, vomiting)
Galactokinase Deficiency
Galactokinase
—> leads to accumulation of Galactitol
Classic Galactosemia
Galactose-1-phosphate-uridyltransferase
—> toxin buildup leads to failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, e. coli sepsis in neonates
PDC Deficiency
Pyruvate Dehydrogenase Complex
—> causes buildup of pyruvate, shunted to lactate (via LDH) and alanine (via ALT)- neurologic defects, lactic acidosis, high serum alanine
Lactose Intolerance
Lactase
Bloating, cramps, flatulence, osmotic diarrhea
Congenital Hyperammonemia
N-acetylglutamate synthase
Required co-factor for carbamoyl phosphate synthetase I
OTC Deficiency
Ornithine Transcarbamylase
most common urea cycle disorder, leads to increased blood and urine orotic acid, DECREASED BUN
Phenylketonuria
Phenylalanine Hydroxylase (enzyme) OR Tetrahydrobiopterin (cofactor for conversion to tyrosine)
intellectual disability, growth retardation, seizures, fair skin, eczema, “musty” body odor
Maple Syrup Urine Disease
a-ketoacid dehydrogenase
blocked degradation of isoleucine, leucine, and valine
severe CNS defects, intellectual disability, and death.
Alkaptonuria
Homogentisate oxidase
Buildup of homogentisic acid–> Dark connective tissue, brown pigmented sclerae, black urine upon prolonged air exposure, arthralgias
Homocystinuria
Cystathione synthase
Excess homocysteine buildup–> homocysteine in urine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation (downward and inward), thrombosis, atherosclerosis
Cystinuria
Defective Reabsorption in PCT of Cysteine, Ornithine, Lysine, and Arginine (COLA)
Von Gierke Disease (type I GSD)
Glucose-6-Phosphate
Severe fasting hypoglycemia, glycogen buildup, increased lactate, increased triglycerides, increased uric acid, hepatomegaly
Pompe Disease (type II GSD)
Lysosomal a-1,4,-glucosidase (acid maltase)
Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, death
Cori Disease (type III GSD)
a-1,6-glucosidase (debranching enzyme)
symptomatically presents as milder form of Von Gierke- hypoglycemia, glycogen buildup, increased lactate, increased triglycerides, increased uric acid, hepatomegaly
McArdle Disease (type V GSD)
Glycogen Phosphorylase (myophosphorylase)–> skeletal muscle
increased muscle glycogen, painful muscle cramps, myoglobinuria with strenuous exercise, arrhythmia (due to electrolyte abnormalities)
Fabry Disease
a-galactoside A
Buildup of Ceramide trihexoside
X-linked recessive (only this and Hunter are XLR- all other board relevant LSDs are AR) Peripheral neuropathy, angiokeratomas, CV/Renal disease
Gaucher Disease
Glucocerebrosidase (B-glucosidase)
Buildup of Glucocerebroside
Most common LSD- hepatosplenomegaly, pancytopenia, aseptic necrosis of femur, bone crises, lipid-laden macrophages
Niemann-Pick Disease
Sphingomyelinase
Buildup of Sphingomyelin
Progressive neurodegeneration, hepatosplenomegaly, foam cells, “cherry-red” spot on macula
Tay-Sachs Disease
Hexosaminidase A
Buildup of GM2 ganglioside
Progressive neurodegeneration, developmental delay, “cherry-red” spot on macula, lysosomes with onion skin, NO HEPATOSPLENOMEGALY, UNLIKE NIEMANN-PICK
Krabbe Disease
Galactocerebrosidase
Buildup of Galactocerebroside and psychosine
Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Metachromatic leukodystrophy
Arylsulfatase A
Buildup of Cerebroside sulfate
Central and peripheral demyelination with ataxia and dementia.
Hurler Syndrome
a-L-iduronidase
Buildup of heparan sulfate and dermatan sulfate
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly AUTOSOMAL RECESSIVE (Hunter-very similar disease is XLR)
Hunter Syndrome
Iduronate Sulfatase
Buildup of heparan sulfate and dermatan sulfate
Developmental delay, gargoylism, airway obstruction, hepatosplenomegaly, aggressive behavior NO CORNEAL CLOUDING—> HUNTERS NEED TO SEE THEIR PREY
UNLIKE HURLER-> XLR UNLIKE MOST OTHER LSDS, WITH EXCEPTION OF FABRY
Systemic Primary Carnitine Deficiency
Defective Long Chain Fatty Acid transport
—>leads to toxic accumulation of long chain fatty acids–> weakness, hypotonia, hypoketotic hypoglycemia
Medium chain acyl-CoA dehydrogenase deficiency
Medium chain acyl-CoA dehydrogenase- Defective fatty acid oxidation
accumlation of 8-10 carbon fatty acyl carnitines in blood and hypoketotic hypoglycemia
can present with vomiting, lethargy, seizures, coma, and liver dysfunction
Type I Dyslipidemia
Lipoprotein lipase deficiency OR altered Apo C-II
Hyperchylomicronemia
causes pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas, creamy layer of blood
Type IIa Dyslipidemia
Absent or defective LDL receptors
familial hypercholesterolemia
accelerated athersclerosis (possible MI before age 20), Achilles xanthomas, corneal arcus
Type IV Dyslipidemia
Hepatic overproduction of VLDL
Hypertriglyceridemia
can cause acute pancreatitis
