Disorder Of Amino Acid Metabolism

Question 0

The manifestations of PKU reflect deficiencies in tyrosine

Hormones/substances that defend on tyrosine as a raw material

Answer 0

Thyroid hormone

Melanin

Catecholamines (dopamine, norepinephrine, epinephrine)

Question 1

Normally, PHENYLALANINE is converted into TYROSINE.

TYROSINE becomes essential and PHENYLALANINE builds up, leading to excess phenylketonuria in urine:

• phenyl acetate
• phenyl lactate
• phenyl pyruvate

Manifestations: mental retardation, growth retardation, fair skin, eczema, musty body odor

Tx: ⬇️ phenylalanine and ⬆️ tyrosine in diet

Answer 1

Phenylketonuria

In PKU, there is ⬇️ phenylalanine hydroxylase or tetrahydrobiopterine cofactor

Question 2

Congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine

Resulting alkapton bodies cause urine to turn black on standing

Also, the connective tissue is dark (ochronosis)

Benign disease but may have debilitating arthralgias

Answer 2

Alkaptonuria

Question 3

Pigmentation of the sclera

Answer 3

Osler’s sign

Question 4

Congenital deficiency of either of the ff:

• TYROSINASE (ability to synthesize melanin from tyrosine, autosomal recessive)
• defective tyrosine transporters (⬇️ amounts of tyrosine and thus melanin)

Lack of melanin results in ⬆️ risk of skin cancer

Can result from a lack of migration of neural crest cells

Answer 4

Albinism

Question 5

Occurs in 3 forms, all autosomal recessive:

• CYSTATHIONINE SYNTHASE DEFICIENCY (tx: ⬇️Methionine, ⬆️cysteine, ⬆️B6 and ⬆️folate in the diet
• ⬇️affinity for cystathionine synthase for pyridoxal phosphate (tx: ⬆️⬆️B6 in diet)
• HOMOCYSTEINE METHYLTRANSFERASE DEFICIENCY

all forms result in excess homocysteine and cysteine becomes essential

Can cause mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward) and atherosclerosis (stroke and MI), stroke in the the young (work up: homocysteinuria test, tx: B6)

Answer 5

Homocysteinuria

Question 6

Common inherited defect of renal tubular amino acid transporter for cysteine, ornithine, lysine and arginine in the PCT of the kidneys

Excess cysteine in urine can lead to precipitation of cysteine kidney stones and causes stag horn calculi

Tx: Acetazolamide to alkalinize the urine

Answer 6

Cysteinuria

Question 7

Blocked degradation of branched amino acids (isoleucine, valine, leucine) due to a deficiency in a-Ketoacidosis dehydrogenase

Causes an ⬆️a-Ketoacidosis in the blood, especially leucine

Causes severe CNS defects, mental retardation and death

Answer 7

Maple syrup urine disease