50. Amino acidopathies

Question 1

Phenylketouria

Answer 1

PKU
AR inheritance
Elevated phenylalanine,-pyruvate,-lactate,-acetate
Sx: hypopigmentation (lack of melanin), CNS.
Phenylalanine hydroxylase (PAH) defect.
Phenyl–>tyrosine disrupted.
Maternal PKU: fetus affected.

Dihydrobiopterin (BH2) deficiency also.
BH4 is used in 3 different rxns: thyrosine synthesis (PAH), catacholamin synthesis and serotonin synthesis).
BH4 is reduced from BH2.
BH2 is synthesized by BH2 synthase

Question 2

Methylmalonic acidemia

Answer 2

AR inheritance.
SX: vomiting, hyperammonemia, HM, developmental
Tx: vit.B12 therapy
Defective methylmalonyl CoA mutase affects leucine metabolism.

Vit.B12 deficiency: needed for methylmalonyl –> succinyl CoA

Question 3

Albinism

Answer 3

AR inheritance. 
Tyrosinase deficiency (tyrosine --> melanine)

Question 4

Alkaptonuria

Answer 4

AR inheritance.
Defect in homogenistic acid (HA) oxidase (disrupted tyrosine metabolism but not melanine).
Sx: onset 40s, darening of urine, dark pigment deposits on joints, severe arthritis.
Tx: diet low in protein (phenyl and tyrosine)

Question 5

Maple syrup urine disease

Answer 5

AR inheritance.
Deficiency in BCKD.
Accumulation of alpha-keto acids.
Sx: sweet odor urine, feeding prob, vomiting, acidosis, mental and physical, death.

Backed up L/I/V disrupts long-neutral amino transport (phenyl and tyro also transported).

Tx: synthetic formual with reduced branched aa (they are essential). must be tx’d w/in 24 hrs.

Question 6

Isovaleryl acidemia

Answer 6

Isovaleryl CoA DH deficiency (leucine affected).
Isovaleryl CoA can react with carnitine to be excreted –> leads to carnitine depletion.

NAG-synthase in urea cycle inhibited.

Question 7

Mdeium or short fatty acyl CoA DH deficiency

Answer 7

Accumulation of isobutyryl or methyl-butyryl CoA (valine and isoleucine metabolites)

Question 8

Propionyl acidemia

Answer 8

Propionyl CoA carboxylase defect or biotin defect.
Propionyl also react with carnitine for excretion.

Urea cycle inhibited (NAG-synthase) –> ketoic hyperglycemia.

Question 9

Homocystininuria

Answer 9

AR inheritance.
Deficiency in cystathionin beta-synthase (disrupted homocysteine –> cysteine).
Elevated levels of homocysteine.
Sx: nearsightedness, blood clotting, skeletal abnormalities (pectus excavatum), osteoporosis, premature arterial dz, mental.