Amino Acid Diseases Flashcards
Due to low phenylalanine hydroxylase or tetrahydrobiopterin (BH4) cofactor
PKU
Tyrosine becomes essential.
PKU
Findings: intellectual disability, growth retardation, seizures, fair complexion, eczema
PKU
and musty body odor.
tetrahydrobiopterin supplementation is needed
PKU
Disorder of aromaticamino acid metabolism
PKU
causes musty body odor
patients must avoid the artificial sweetener aspartame
PKU
Blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to deficiency of branched-chain
α-ketoacid dehydrogenase (needs Vit. B1).
Maple Syrup Urine
Increased α-ketoacids in the blood, especially those of leucine.
Maple Syrup Urine
thiamine (Vit. B1) supplementation is needed
Maple Syrup Urine
vomiting, poor feeding, urine smells like burnt sugar. Causes severe CNS defects, intellectual disability, death.
Maple Syrup Urine
Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
pigment-forming homogentisic acid builds up in tissue
GRAYISH-BLUE-ASHEY skin lesions
Alkaptonuria
I’ll capture all of you. I’m TyRed of FUMing over you turning the gentle homo black and blue”
bluish-black connective tissue, ear cartilage, and sclerae (ochronosis);
urine turns black on prolonged exposure to air.
May have debilitating arthralgias (homogentisic acid toxic to cartilage).
Alkaptonuria
Osteoporosis, Marfanoid habitus,
Ocular changes (downward and inward lens subluxation), Cardiovascular effects
(thrombosis and atherosclerosis stroke and MI),
kyphosis,
intellectual disability,
fair complexion
Homocystinuria
lens subluxes “down and in”
(vs Marfan, “up and out”).
a condition that leads to hypercoagulability and thromboembolic occlusion.
Can cause acute coronary syndrome in Children (MIs)
Ectopic lens
Mental retardation
homocystinuria
Hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine (COLA).
Cystinuria
Excess cystine in the urine can lead to recurrent precipitation of what stones
Hexagonal
Most commonly present in infancy with poor feeding, vomiting,
hypotonia,
high anion gap metabolic acidosis,
hepatomegaly,
seizures.
Organic acid accumulation: ketoacidosis &/or hyperammonemia
Propionic Acidemia or Methylmalanic Acidemia ---------- Deficiency of propionyl-CoA carboxylase Deficiency of methylmalonyl-CoA mutase or vitamin B12
Maple syrup = NO AMMONEMIA
Treatment: low-protein diet limited in Valine, Odd-chain fatty acids, Methionine, Isoleucine, Threonine (VOMIT).
Propionic Acidemia
Methylmalanic Acidemia
or
Maple Syrup
*technically Thymadine and Uracil are not supposed to be given either
Methylmalanic Acidemia is caused by
what enzyme
or
What Vitamin Deficiency?
Deficiency of
methylmalonyl-CoA mutase
or
vitamin B12
Propionic Acidemia is caused by
what enzyme and vitamin deficiency
Deficiency of propionyl-CoA carboxylase
Vit B7 Biotin dependent
_____ is caused by impaired transport of neutral amino acids in the small intestine and proximal tubule of the kidney. Symptoms include pellagra-like skin eruptions and cerebellar ataxia, which occur as a result of _____ deficiency.
Hartnup disease
niacin (Vit B3)
a urea cycle enzyme that produces urea and ornithine from arginine. A deficiency results in progressive spastic diplegia (paresis), growth delay, and abnormal, choreoathetoid movements.
Present with no (or mild) hyperammonianemia.
Arginase
Treatment includes an arginine-free, low-protein diet.
Deficiencies of vitamins ______(3) are associated with hyperhomocysteinemia, which in turn is associated with atherosclerosis and thrombotic events.
B6, B12, and folate (B9)
Orotic aciduria (AR) disorder of de novo pyrimidine synthesis that occurs due to a defect in ________ enzyme.
Children typically present with physical and mental retardation, megaloblastic anemia elevated urinary orotic acid No ammonemia
______ supplementation can improve symptoms
uridine 5’-monophosphate (UMP) synthase
Uridine
(Uridine to UMP via nucleoside kinases)
The hydroxylation of proline and lysine residues in collagen helps it attain its maximum tensile strength. This process occurs in the ________ and requires vitamin C as a cofactor. Impaired collagen synthesis resulting from vitamin C deficiency (scurvy) can lead to fragile vessels, predisposing to _______, ecchymosis, and petechia.
rough endoplasmic reticulum
Bleeding gums
*coiled corkscrew hair can also be seen (nasty)
________ can be used to treat homocystinuria, which is caused by a defect in _________.
This condition is characterized by elevated homocysteine levels, ectopia lentis, intellectual disability, Marfanoid body habitus, and increased occurrence of thromboembolic events.
Pyridoxine (vitamin B6)
Cystathionine synthase (vitamin B6-dependent)
Cysteine becomes essential
Homocysteinuria
Can have cardiovascular effects thrombosis atherosclerosis stroke MI
Homocysteinuria
Can cause Hypermethonemia
Homocysteinuria
Pyruvate carboxylase catalyzes the initial step in ___ by converting pyruvate to oxaloacetate.
gluconeogenesis
Requires B7 (Biotin)
Ornithine transcarbamylase catalyzes the combination of ornithine and carbamoyl phosphate to form____ in the urea cycle.
citrulline
- This reaction occurs within the mitochondria.
Ornithine transport into mitochondria is necessary for the urea cycle. Defects typically cause neurological damage due to hyperammonemia.
______ restriction improves this condition by reducing the amount of amino acid turnover.
Protein
Alanine transfers amino group to ____ for glucose synthesis as well
Alpha Ketoglutarate
Patients with ___ disorders typically have discrete episodes of vomiting, tachypnea, and confusion/coma secondary to hyperammonemia (a metabolic emergency).
urea cycle (Arginase deficiency)
*Ornithine transcarbamylase deficiency is the most common disorder of the urea cycle
Examination shows scaly, erythematous skin lesions in sun-exposed areas and cerebellar ataxia.
Child is pruritic and irritable.
Laboratory evaluation shows increased levels of neutral amino acids in the urine.
Diagnosis
Hartnup
Vit B3 deficiency (Niacin)
