PATH - Catecholamine synthesis/tyrosine catabolism Defeciencies

Question 1

Phenylketonuria (PKU)

Answer 1

Autosomal recessive

Due to DEC phenylalanine hydroxylase or
DEC tetrahydrobiopterin cofactor (malignant PKU).

Findings: intellectual disability, growth retardation, seizures, fair skin, eczema, *musty body odor.

Treatment: DEC phenylalanine and INC tyrosine in diet, tetrahydrobiopterin supplementation.

PKU patients must avoid the artificial sweetener
aspartame, which contains phenylalanine.

Question 2

Maternal PKU

Answer 2

lack of proper dietary therapy
during pregnancy.

Findings in infant:
microcephaly, intellectual disability, growth retardation, congenital heart defects.

Question 3

Maple syrup urine disease

Answer 3

Autosomal recessive

Blocked degradation of *branched amino acids (Isoleucine, Leucine, Valine) due to DEC branched-chain α-ketoacid dehydrogenase
(B1).

Causes INC *α-ketoacids in the blood, especially those of leucine

Causes severe CNS defects, intellectual disability, and death.

Presentation: vomiting, poor feeding, *urine smells like maple syrup/burnt sugar

TX: restriction of isoleucine, leucine, valine in diet, and thiamine supplementation

I Love Vermont maple syrup from maple trees (with B1ranches).

Question 4

Alkaptonuria

Answer 4

Autosomal recessive

Congenital deficiency of *homogentisate oxidase in the degradative pathway of tyrosine to fumarate–>pigment-forming *homogentisic acid accumulates in tissue

Usually benign

Findings: bluish-black connective tissue and sclerae (ochronosis); urine turns black on prolonged
exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).

Question 5

Homocystinuria

Answer 5

all autosomal recessive

All forms result in excess *homocysteine.

Findings: INC INC INC homocysteine in urine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation (downward and
inward), thrombosis, and atherosclerosis (stroke
and MI).

Types:

• Cystathionine synthase deficiency
• DEC affinity of cystathionine synthase for pyridoxal phosphate
• Methionine synthase (homocysteine
  methyltransferase) deficiency

Question 6

Cystinuria

Answer 6

Autosomal recessive

Hereditary defect of renal PCT and intestinal
amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine,
and Arginine (*COLA).

Excess cystine in the urine can lead to recurrent
precipitation of hexagonal cystine stones

Urinary *cyanide-nitroprusside test is diagnostic.

TX: urinary alkalinization (eg, potassium citrate, acetazolamide) and chelating agents (eg, penicillamine)  solubility of cystine stones; good hydration