AA Disease Flashcards
What is Hartnup disease?
Neutral amino aciduria. Defective neutral amino acid transporter. Leads to tryptophan in urine. Niacin given to help with pellegra like symptoms (B3)
What is Cystinuria?
COAL transporter in lumen (cystine, ornithine, arginine, lysine). Excretion of cystine in urine. Drink lots of water to solubilize cystine
Alanine aminotransferase or aspartate aminotransferases in blood (ALT and AST)
Cell damage in liver
What is hyperammonemia?
Elevated levels of ammonia often occurring in chronic liver disease or inherited metabolic disorder
Ammonia toxicitiy
Depletes alpha ketoglutarate, ATP and NAD(P) via glutamate dehydrogenase. Glutamate is also an excitatory NT.
What are two diseases leading to hyperammonemia?
N-acetylglutamate synthase (NAGS) deficiency and CPS I deficiency
What is ornitine transcarabmoylase (OTC) defiency
Most common urea cycle disorder, linked to X-chromosome. Increased orotic acid and uracil in blood and urine
What is citrullinemia?
Caused by arginiosuccinate synthetase deficiency. A distal urea disorder, not severe as Citrulline can be excreted
What is arginiosuccinic aciduria (ASA)?
Argininosuccinate lyase is deficient. Not a problem because argnininosuccinate can be excreted
What is argininemia?
Arginase deficiency. Arginine can be excreted. Extremely rare but can lead to developmental abnormality
Assay citrulline. Absent or trace. Low orotic acid. What’s wrong?
CPS I or NAGS deficiency
Assay Citrulline. Absent or trace. High urine orotic acid. What diagnosis?
OTC deficiency
Assay citrulline. 100-300 uM. High levels of plasma arginosuccinate. What’s wrong?
AL deficiency
Assay citrulline. Very high levels of citrulline. What’s diagnosis?
AS deficency.
What is nonketotic hyperglycinema?
Defect in glycine cleavage complex (glycine synthase) preventing production of ammonia and carbon dioxide. High glycine in blood.
What is histidinemia?
Deficiency in histidase. High levels in blood and urine of histidine.
What is maple syrup urine disease?
Defective or missing branched-chain alpha-keto acid dehydrogenase
What is tyrosinemia II?
Missing tyrosine aminotransferase (important in the process of making fumarate and acetoacetate from phenylalanine/tyrosine). Accumulation of tyrosine
What is tyrosinema I?
Defect in fumarate and acetoacetate steps of trp/phe degredation. Leads to liver and renal disease. Not associated with as significant of a tyrosine build up
What is alcaptonuria?
Absence of homogentisate oxidase which leads to accumulation of homogentisate in urine. Leads to dark urine and arthritis.
What is albinism?
Defect in tyrosine metabolism leading to deficient melanin production.
What is phenylketonuria?
Defect in phenylalanine conversion to tyrosine conversion perhaps in phenylalanine hydroxylase
What are two potential causes of phenylketonuria?
Deficiency of phenylalanine hydroxylase (classical) or defect in tetrahydrobiopterin (BH4, also referred to as biopterin) cofactor synthesis (non-classical)
Non-classical PKU (i.e. BH4 issues) is determined by what as compared to classical PKU?
Dopamine levels (catecholamines and serotonin levels) are decreased
What is homocystinuria?
High levels of homocysteine in plasma/serum due to cystathionine synthase deficiency or reduced affinity for B6 cofactor. Could also be due to remethylation pathway deficiency (methionine synthase). B6,B12, and Folate help (THF is involved in methionine recovery).
What is methylmalonic acedemia (MMA)?
Deficiency in methylmalonyl CoA mutase which leads to accumulation of methylmalonic acid. Accumulation from met, val, Ile, and Thr
4 causes for homocystinuria
Cystathionine synthase deficiency. Loss of pyridoxal phosphate. methionine synthase def. defin methylene THF reductase
Folic acid deficiency
Hematopoietic and neurological symptoms
What is pernicious anemia?
Could be because of intrinsic factors or B12. Lead to megaloblastic anemia or neurological defect.
What is neuropsychiatric porphyria?
Accumulation of ALA and PBG in cells.
What is cutaneous porphyria?
Accumulation of porphyriogens in skin and tissues leading to photosensitivity.
What is acute intermittent porphyria (AIP)?
PBG and ALA in the urine. Caused by deficiency in PBG demainase (catalyzes porphobilinogen to hydroxymethylbilane)
What is porphyria cutaneous tarda (PCT)?
Defect in uroporphyrinogen decarboxylase which converts uroporphyrinogen III to coproporphyrinogen III. Accumulation leads to photosensitivity.
What is jaundice?
Accumulation of bilirubin (hyperbilirubinemia). Caused by excess production or decreased excretion.
What are the three types of jaundice?
Hemolytic or preheptic jaundice (production exceeds liver conjugation capacity). Hepatocellular or intrehepatic jaundice (liver damage). Obstructive or Posthepatic jaundice (decreased secretion).
What is neonatal jaundice?
Liver not fully developed
