Urine Screening for Metabolic Disorders

Study Notes

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.