AA metabolism

Question 1

Cistinuria

Cause:
Result:
Sx:
Tx: 
Dx:
Keywords:

Answer 1

Cause: Failure of COAL transporters in the proximal tubule of the kidneys
Result: No absorption of dibasic AA (Cystein, ornithine, arginine, & lysine)
Sx: High Cyst in urine>stones (flat/hex) > abrasion > bleeding (nephrolithiasis)

Question 2

Hartnups Disease

Answer 2

Cause: Failure of Kidney amino acid transports for neutral amino acids, like Tryptophan
Result: Red Tryp in serum, inc in urine
Sx: Pellagra (NAD+ def), dementia, Diahrrea, Dermtitis and Death (4 D’s)
Tx: High protein + Dietary niacin (treats NAD+ def), avoidance of sun exposure

Question 3

Phenylketonuria Type I

Answer 3

Cause: Deficiency in the Phenylalanine Hydroxylase enzyme/ or mutation > less affinity to cofactor BH4
Result: Buildup of Phenylalanine, deficiency of Tyrosine (becomes essential)
Sx: high phenylalanine > phenyl-lactate, phenylacetate, & phenylpyruvate (mousey smell), CNS defects (retardation, seizures, delayed dev: red NT, myeline, and brain AA transporters)
Tx: Strict diet, supp tyrosine (becomes essential), no phenylalanine (meats, diary, eggs, artsweeteners)
Dx:
Keywords: infant screening (heel prik, mass spec, Guthrie Assay). Autosomal recessive disorder.

Question 4

Maternal PKU (type I)

Answer 4

Cause: Mom w/def phynelalanine hydroxylase > high phen in foetus
Result: tetratogenic effect on foetus
Sx: CNS defect, microcephaly, congenital heart disease in fetus

Question 5

PKU Types II & III

Answer 5

Cause: Type II: def in Dihydrobiopterin Reductase (BH2>BH4). Type II: defect in BH$ synthesis from GTP
Result: Decrease in BH4 levels and thus Phenylalanine Hydroxylase activity
Sx: More detrimental than type I More pathwyas use BH4 (dopamine, serotonin, catecholamins, etc
Tx: Diet low in Phe and supplements for biopterin and precursors for NT

Question 6

Alkaptonuria

Answer 6

Cause: Deficiency in Homogentisate Oxidase enzyme
Result: build up of homogenistate Oxidase > dark urine, & Ochonosis > dark collagenous bones and cartilage, joint arthritis, metabolic acidosis
Tx: Dietary restriction of Phenylalanine and Tyrosine
Keywords: Blue-ish/black discoloration of the sclera and auriculum

Calcification of arterial walls

Question 7

Tyrosinemia Type I

Answer 7

Cause: Deficiency in Fumerylacetoacetate Hydrolase enzyme
Result: Buildup of Fumerylacetoacetate
Sx: Death by 1y/o due to Liver and Kidney failure

Question 8

Tyrosinemia Type II

Answer 8

Cause: Deficiency in Tyrosine Aminotransferase enzyme
Result: Buildup of Tyrosine
Sx: Skin & eye lesions, though CNS defects are more of a concern
Tx: Patients may respond to a low phenylalanine diet

Question 9

Maple Syrup Urine Disease

Answer 9

Cause: Deficiency of the Branched Chain alpha-Keto Acid Dehydrogenase enzyme/ or milder form in kids due to low affinity of enzyme to B12 cofactor
Result: Buildup of Branched-chain amino acids and their respective Keto-Acids
Sx: metabolic acidosis, maple urine, CNS defects: hypo/hyper tonia, seizures, encephalopathy, & metabolic coma. In 4th-7th day: poor feeding, irritability, vomiting, lethargy
Tx: Thiamine to treat low affinity of cofactor TPP. Difficult to treat as all BCAA are essential & are in most foods. Reduce PA

Question 10

Methylmalonic Aciduria

Answer 10

Cause: Deficiency in the MethylMalonyl-CoA Mutase enzyme; can also be indicative of Vitamin B12 deficiency
Result: Inability to make Succinyl-Coa from MM-CoA > metabolic acidosis (MM acidaemia/aciduria) due to acc. Of MM acid
Sx: MM-CoA in branched chain FAs in CNS > seizures, encephalopathy. MM-CoA > methylmalonic acid > metabolic acidosis
Tx: Vit B12 (Cobalamin) supp to treat red affinity. Feeding by gastrostomy tube, diet low in BCAA
Dx:
Keywords:

Question 11

Homocystinuria

Answer 11

Cause: Deficiency in the Cystathionine Beta-Synthase enzyme, B12, Tetrahydrofolate (Folic Acid) or PLP (VitB6)
Result: Inability to synthesize Cystathionine from Homocysteine –> buildup of homocysteine/excess in plasma/urine
Sx: build up homocystein > disrupt CT > ectopia lentis (dislocated lens). skeletal abnormalities, osteoporosis, mental retardation, arterial disease (formation of homocystein Thiolactone, paltlet aggregation, oxidation stress, apo A-1).
Tx: Vit B6 (pyroxine) > PLP, folic acid (B9), B12
Dx:
Keywords: homocysteine > OX > Homocystine in urine