Metabolic Disorders and Renal Diseases

• What is the overflow type of urine analysis?

  It results from the disruption of a normal metabolic pathway causing increased plasma concentrations of non-metabolized substances.
• What causes the renal type of urine analysis?

  It is caused by malfunctions in the tubular reabsorption mechanism.
• What are the causes of abnormal metabolic constituents in urine?

  • Disruption of enzyme function
  • Failure to inherit the gene to produce an enzyme
  • Lifetime medication (supportive treatment)
• What are some abnormal metabolic constituents detected in routine urinalysis?


  • Color
  • Odor
  • Crystals (e.g., Homogentisic acid, Melanin, Indican, Porphyrins)
• What are the major disorders of protein and carbohydrate metabolism associated with abnormal urinary constituents?

  • Overflow Inherited Metabolic Disorders
  • Renal Disorders
  • Examples include Phenylketonuria, Tyrosinemia, Alkaptonuria, and Maple syrup urine disease
• What is Phenylketonuria (PKU)?

  It is the presence of abnormal phenylalanine metabolites in the urine.
• What happens if Phenylketonuria is undetected?

  It results in Phenylpyruvic oligophrenia.
• Who discovered Phenylketonuria and when?

  Ivan Følling discovered it in 1934 in Norway.
• What enzyme is deficient in Phenylketonuria?

  The enzyme deficient is Phenylalanine hydroxylase.
• What is the common screening test for most amino acidurias?

  The Ferric chloride tube test is commonly used.
• What are the tests for Phenylketonuria?

  • Phenylalanine Blood Level: Increased 2-6 weeks prior to urinary excretion.
  • Phenylpyruvic Acid Urine Test: Based on ferric chloride reaction.
  • Ferric Chloride Tube Test: (+) result shows stable green/blue green.
  • Guthrie Test: Uses beta-2-thienylalanine to inhibit bacterial growth.
• What is Tyrosyluria/Tyrosinemia characterized by?

  It is characterized by the accumulation of excess tyrosine in the plasma.
• What causes Tyrosyluria?

  It can be caused by an inherited defect or metabolic defect due to liver disease.
• What are the types of Tyrosyluria and their enzyme deficiencies?

  • Type 1: Fumarylacetoacetate hydrolase (FAH) deficiency.
  • Type 2: Tyrosine aminotransferase deficiency.
  • Type 3: p-hydroxyphenylpyruvic acid oxidase deficiency.
• What is the result of the nitrosonaphthol test for Tyrosyluria?

  The result is an orange-red color.
• What is Melanuria associated with?

  It is associated with increased urinary melanin and darkening of urine after exposure to air.
• What are the tests for Melanuria?

  • Ferric Chloride Tube Test: Produces gray or black precipitate.
  • Sodium Nitroprusside Test: Produces red color.
  • Tandem mass spectrometry (MS/MS): Confirms presence of melanin.
• What is Alkaptonuria characterized by?

  It is characterized by darkened urine after becoming alkaline from standing at room temperature.
• What enzyme is deficient in Alkaptonuria?

  The enzyme deficient is homogentisic acid oxidase.
• What are the tests for Alkaptonuria?

  • FeCl3 Test: Transient deep blue color.
  • Clinitest: Yellow precipitate.
  • Urinary Homogentisic Acid Test: Darkening of color upon adding alkali.
  • Ammoniacal Silver Nitrate Test: Produces black urine.
• What amino acids are involved in Maple Syrup Urine Disease (MSUD)?

  The amino acids involved are leucine, isoleucine, and valine.
• What is the characteristic odor of urine in Maple Syrup Urine Disease?

  It has a strong odor resembling maple syrup.
• What are the tests for Maple Syrup Urine Disease?

  • 2,4-dinitrophenylhydrazine (DNPH) reaction: Yellow turbidity or precipitate.
  • MS/MS: Confirms presence of keto acids.
• What are the characteristics of organic acidemias?

  • Isovaleric Acidemia: Sweaty feet odor.
  • Propionic Acidemia: No changes in urine odor.
  • Methylmalonic Acidemia: No changes in urine odor.
• What is the metabolic fate of tryptophan?

  Tryptophan is metabolized in the gut to indole, which is excreted in feces as skatole.
• What is the significance of 5-hydroxyindoleacetic acid (5-HIAA) in urine?

  1. HIAA is a metabolite of serotonin present in urine.
• What are the tests for 5-Hydroxyindoleacetic Acid?

  • Nitroso-naphthol Test: Purple to black color depending on 5-HIAA level.
  • Requires 24h sample with preservative and strict diet.
• What are the characteristics of Cystine Disorders?

  • Cystinuria: Elevated cystine in urine, (+) cystine crystals.
  • Cystinosis: Crystalline deposits of cystine in the body.
  • Homocystinuria: Increase in homocystine throughout the body.
• What is the test for Cystinuria?

  The Cyanide-nitroprusside Test shows a red-purple color.
• What is Porphyria?

  • Collective term for disorders of porphyrin metabolism.
  • Problems with heme synthesis.
• What are the characteristics of Mucopolysaccharide Disorders?

  • Hurler syndrome: Abnormal skeletal structure and severe mental retardation.
  • Hunter syndrome: Mucopolysaccharides accumulate in the cornea.
  • Sanfilippo syndrome: Mental retardation.
• What is the test for Mucopolysaccharide Disorders?

  Acid-albumin test shows turbidity after 30 mins.
• What is the cause of Lesch-Nyhan Disease?

  • Failure to inherit the gene for HGPRT enzyme.
  • Results in increased uric acid levels.
• What are the characteristics of carbohydrate disorders?

  They include melituria, pentosuria, galactosuria, and lactosuria.
• What are the four types of renal disease?

  • Glomerular (immune mediated)
  • Tubular (infection)
  • Interstitial (infection)
  • Vascular (reduction in renal perfusion)
• What are the classifications of renal disease?

  • Glomerular Disorders: Associated with the glomerulus.
  • Tubular Disorders: Affecting renal tubules.
  • Interstitial Disorders: Affecting the interstitium.
  • Renal Failure: Exists in acute and chronic forms.
• What are the two main types of tubular function disruptions mentioned?

  Actual damage to the tubules and metabolic or hereditary disorders
• What are the functions affected by tubular disorders?

  Reabsorption and secretion
• What can cause disorders affecting tubular function?

  Systemic conditions that affect the tubular reabsorptive maximum (Tm)
• What is tubulointerstitial disease?

  Disorders affecting the interstitium that also affect the tubules