Urine Screening for Metabolic Disorders

Urine Screening for Metabolic Disorders

• Purpose: Urine screening aids in detecting metabolic disorders.
• Types of metabolic disorders: Amino acid disorders, porphyrin disorders, mucopolysaccharide disorders, purine disorders, and carbohydrate disorders are covered.
• Importance of newborn screening: Urine and blood tests are used to detect inborn errors of metabolism (IEMs) in newborns.
• Common inborn error of metabolism in the Philippines: MSUD (maple syrup urine disease) is the most common.

Amino Acid Disorders

• Phenylketonuria (PKU): Most common aminoaciduria, linked to severe mental retardation if untreated. Characterized by:
  • Fair complexion due to reduced melanin production.
  • Elevated phenylalanine in blood (can be detected early).
  • Urine with a distinctive mousy odor due to increased phenylpyruvate.
• Tyrosyluria: Secondary to tyrosinemia, featuring:
  • Urinary metabolites such as p-hydroxyphenylpyruvic and p-hydroxyphenyllactic acid.
  • Often seen in premature infants.
  • In severe liver diseases, tyrosine and cystine crystals may be present.
• Melanuria: Darkening urine due to melanin production deficiencies. Caused by:
  • Deficiency in melanin production.
  • Darkening of urine exposed to air.
• Albinism: Lack of melanin in skin and eyes.
• Alkaptonuria: Inability to process homogentisic acid, leading to:
  • Darkening of urine after alkalinization
  • Accumulation of homogentisic acid in blood, tissues, and urine.
  • Potential for arthritis later in life due to deposition of brown pigment in cartilage.
• Branched-Chain Amino Acid Disorders (MSUD): Results from deficient enzyme function with:
  • Clinical symptoms like failure to thrive.
  • Strong maple syrup odor due to excessive ketoacids.
  • Accumulation of leucine, isoleucine, and valine.
• Organic Acidemias: Generalized symptoms include:
  • Severe illness
  • Vomiting
  • Metabolic acidosis
  • Hypoglycemia
  • Elevated serum ammonia
• Types of organic acidemias: Isovaleric acidemia, Propionic acidemia, and Methylmalonic acidemia are examples.
• Indicanuria: Excess indole in the intestine results in blue urine upon exposure to air. Often related to intestinal obstruction or bacterial abnormalities.
• 5-Hydroxyindoleacetic Acid (5-HIAA): Elevated levels could stem from argentaffinoma, an endocrine tumor and can be detected through a 24-hour urine sample preserved with acid.
• Cystinuria: Defect in reabsorbing cystine, ornithine, lysine, and arginine. Increased risk of kidney stones.
• Cystinosis: Inborn error of metabolism resulting in crystal deposition in cells and organs (e.g., cornea, bone marrow). Two main types, infantile and late onset.
• Homocystinuria: Defect in the cystathionine beta-synthase enzyme, leading to various clinical issues, like failure to thrive, cataracts, and mental retardation.
• Tests: Various tests are used to diagnose these disorders, including bacterial inhibition tests, tube tests, reagent strips for specific metabolites, and analyses of urine samples.

Porphyrin Disorders

• Porphyrins: Intermediate compounds in heme production.
• Detection: Detected in urine and feces. Key substances include d-aminolevulinic acid (ALA), porphobilinogen, coproporphyrin, protoporphyrin, and uroporphyrin.
• Acquired Porphyrias: Caused by lead poisoning, excessive alcohol, iron deficiency, liver diseases, and kidney conditions.
• Inherited Porphyrias: Result from a missing or defective enzyme in the heme synthesis pathway.

Mucopolysaccharide Disorders

• Mucopolysaccharides: Protein core with numerous polysaccharide branches.
• Excretion: Keratan sulfate, heparan sulfate, dermatan sulfate are excreted in urine.
• Disorders:
  • Hunter's Syndrome: Less severe skeletal structure abnormality, severe mental retardation.
  • Hurler Syndrome: Excessive accumulation of mucopolysaccharides in the cornea and the eye, severe skeletal structure abnormality, severe mental retardation.
  • Sanfilippo's syndrome: Mental retardation.

Purine Disorders

• Lesch-Nyhan syndrome: An inherited purine metabolism disorder resulting from a failure to produce the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). It's characterized by massive excretion of uric acid, motor dysfunction, mental retardation, and a tendency towards self-harm. Orange sand in diapers is a significant indicator.

Carbohydrate Disorders

• Galactosuria: Inability to convert galactose to glucose. Accumulation of galactose can lead to serious complications like failure to thrive, liver dysfunction, cataracts, and mental retardation.

• Other carbohydrate disorders: Lactosuria, fructosuria, and pentosuria are further examples, related to the metabolism of other sugars.