Phenylketonuria (PKU)

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Phenylketonuria (PKU)

• 1 in every 10,000 20,000 births
• Results in mental retardation unless detected
  early. Also Causes fair skin.
• Defect phenylalanine hydroxylase (liver
  kidneys)
• Increased amounts of ketoacids such as
  phenylpyruvic acid

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PKU continued

• Diet changes to prevent excess buildup of plasma
  phenyalanine (PA)
• Blood samples taken for screening after adequate
  ingestion of PA
• Concern shorter hospital stays baby may be
  released before adequate ingestion
• Newborn testing required by law in Texas

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PKU continued

• Phenylpyruvic acid in urine (musty odor) rises
  2-6 weeks after increased blood PA. Used to
  monitor diet, screen pregnant PKU women, or
  follow-up on questionable PKU test results

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Tyrosinemia

• Type I Liver Damage and Fanconis syndrome
  (generalized renal tubular failure)
• Type II defective tyrosine aminotransferase
  (transaminase) deposits of tyrosine affecting
  skin and eyes.
• Both types high level of tyrosine in blood and
  urine

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Alkaptonuria

• Enzyme defect homogentisic acid oxidase
• Increased homogentisic acid in blood, urine, and
  tissues
• Urine darkens after becoming alkaline from
  prolonged time at room temperature
• Doesnt show up until later childhood. Later
  brown pigment deposits in tissues may lead to
  arthritis and liver and heart disorders

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Tryptophan disorders

• Indican source?
• Indole source?
• Certain disorders of intestine (obstruction,
  abnormal bacteria, malabsorption syndromes, rare
  inherited Hartnup disease) have increased amounts
  of tryptophan which goes to indole which is
  absorbed and goes to liver and becomes indican .

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Indican in urine colorless until oxidized by air
to form indigo blue.
Blue Diaper Syndrome Hartnup Disease affects
not only intestinal absorption of tryptophan but
also renal tubular reabsorption of other amino
acids also
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5-HIAA5-hydroxyindoleacetic acid

• Argentaffin Pathway in intestine
• Serotonin produced and carried by blood platelets
• Argentaffinomas
• Dietary restrictions prior to testing sample
  collection

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Branched chain amino acid Disorders

• Branched chain a. acids have methyl group that
  branches from main carbon chain
• 2 types
• Accumulation of 1 or more early pathway acid
  degradation products ex. MSUD
• Accumulation of organic acids produced further
  down in the metabolic pathway ex. Organic
  acidemias
• Both have ketoaciduria in newborn

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Maple Syrup Urine Disease

• Rare
• Involves leucine, isoleucine, and valine
• Metabolism begins normally with transamination in
  liver to 3 certain ketoacids
• Deficiency of enzymes needed to break down these
  3 acids

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MSUD continued

• Increased levels of these acids in urine
• a-ketoisovaleric, a-ketoisocaproic, and
  a-keto-ß-methylvaleric acids
• Urine strong odor - maple syrup
• Clinical symptoms failure to thrive within
  one week after birth
• Results severe mental retardation and death
  unless detected early

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Organic Acidemias

• Symptoms severe illness, vomiting,
  hypoglycemia, matabolic acidosis, increased
  ammonia levels
• Example isovaleric acid sweaty feet odor of
  urine. No screening test available for this one.
  Are screens for some of these.

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Disorders of cystine metabolism

• Odor of sulfur may be noticeable in urine

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Cystinosis

• Enzyme defect, inborn error of metabolism
• 3 variations from fatal in infancy to benign
  adult
• Incomplete metabolism of cystine results in
  cystine deposits in tissues
• May also have defect of renal tybuls called
  Fanconis syndrome cant reabsorb a.acids,
  sugar, K, water, etc.

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Cystinuria

• Inherited defect of renal tubular amino acid
  transport
• Increased cystine in urine because tubules cant
  reabsorb
• 2 forms Cystine and lysine involved OR cystine,
  lysine, arginine, and ornithine
• Tends to form calculi (stones) esp. cystine since
  it is the least soluble. May see cystine
  crystals in urine

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Homocystinuria

• 2nd most common metabolic disorder causing
  serious mental retardation
• Increased homocystine
• Homocysteine is an intermediate structure between
  methionine and cysteine
• Homocysteine is unstable in water (and urine) and
  oxidizes to homocystine
• Also increased methionine and other S containing
  amino acids

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