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84 SECTION II BIOCHEmISTRY ``BIOCHEMISTRY—METABOlISM BIOCHEmISTRY ``BIOCHEMISTRY—METABOlISM
Phenylketonuria Due to phenylalanine hydroxylase or Autosomal recessive. Incidence ≈ 1:10,000.
tetrahydrobiopterin (BH 4 ) cofactor Screening occurs 2–3 days after birth (normal at
(malignant PKU). Tyrosine becomes essential. birth because of maternal enzyme during fetal
phenylalanine phenyl ketones in urine. life).
Findings: intellectual disability, growth Phenyl ketones—phenylacetate, phenyllactate,
retardation, seizures, fair complexion, eczema, and phenylpyruvate.
musty body odor. Disorder of aromatic amino acid metabolism
Treatment: phenylalanine and tyrosine in musty body odor.
diet, tetrahydrobiopterin supplementation. PKU patients must avoid the artificial sweetener
aspartame, which contains phenylalanine.
Maternal PKU—lack of proper dietary therapy
during pregnancy. Findings in infant:
microcephaly, intellectual disability, growth
retardation, congenital heart defects.
Maple syrup urine Blocked degradation of branched amino Autosomal recessive.
disease acids (Isoleucine, Leucine, Valine) due to Presentation: vomiting, poor feeding, urine
branched-chain α-ketoacid dehydrogenase smells like maple syrup/burnt sugar. Causes
(B 1 ). Causes α-ketoacids in the blood, severe CNS defects, intellectual disability,
especially those of leucine. death.
Treatment: restriction of isoleucine, leucine, I Love Vermont maple syrup from maple trees
valine in diet, and thiamine supplementation. (with B 1 ranches).
Alkaptonuria Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
pigment-forming homogentisic acid builds up in tissue A. Autosomal recessive. Usually benign.
A
Findings: bluish-black connective tissue, ear cartilage, and sclerae (ochronosis); urine turns black on
prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).
Homocystinuria Causes (all autosomal recessive): All forms result in excess homocysteine.
Cystathionine synthase deficiency HOMOCYstinuria: Homocysteine in
urine, Osteoporosis, Marfanoid habitus,
(treatment: methionine, cysteine, B 6 ,
B 12 , and folate in diet) Ocular changes (downward and inward
affinity of cystathionine synthase for lens subluxation), Cardiovascular effects
pyridoxal phosphate (treatment: B 6 and (thrombosis and atherosclerosis stroke
cysteine in diet) and MI), kYphosis, intellectual disability, fair
Methionine synthase (homocysteine complexion. In homocystinuria, lens subluxes
methyltransferase) deficiency (treatment: “down and in” (vs Marfan, “up and fans out”).
methionine in diet)
Methylenetetrahydrofolate reductase (MTHFR)
deficiency (treatment: folate in diet)
Methionine Cystathionine
synthase synthase
Methionine Homocysteine Cystathionine Cysteine
B B
12 6
Serine
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