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• Renal disorders


  Reabsorption abnormalities occur as a result of renal tubular disease or renal toxins
• Overflow disorders


  Can occur as a result of disruption of a normal metabolic pathway that cannot complete processing metabolites normally. Often an excess of metabolites occurs in the blood and then follows to the urine. This can occur in newborns due to a genetic "inborn error of metabolism (IEM)" related to a missing or defective enzyme.
• Renal disorders


  • Hartnup disease
  • Cystinuria
• Metabolic overflow disorders


  • Infantile tyrosinemia
  • Melanuria
  • Indicanuria
  • 5-HIAA
  • Porphyria
• Inherited overflow disorders


  • PKU
  • Tyrosinemia
  • Alkaptonuria
  • Maple syrup urine disease
  • Organic acidemias
  • Cystinosis
  • Porphyria
  • Mucopolysaccharidoses
  • Galactosemia
  • Lesch-Nyhan disease
• Most babies with metabolic disorders look "normal" at birth. By doing newborn screening, metabolic disorders may be detected even before clinical signs and symptoms are present. And as a result of this, treatment can be given early to prevent consequences of untreated conditions.
• Newborn screening is done by taking a few drops of blood from the baby's heel, blotting on a special absorbent filter card and then sent to a newborn screening center.
• Ideally, newborn screening is done on the 48th-72nd hour of life, but may also be done after 24 hours from birth.
• The Newborn Screening Act of 2004 establishes a national comprehensive newborn screening system to ensure an integrative and sustainable implementation of the government's policy to protect and promote the right to health of the people, including the rights of children to survival and full and healthy development as normal individuals.
• The country currently has four facilities equipped with a laboratory that provides the required tests and programs for newborn screening.
• Disorders screened in the Philippine newborn screening program

  • Congenital Hypothyroidism
  • Congenital Adrenal Hyperplasia
  • Galactosemia
  • Phenylketonuria
  • G-6-PD deficiency
  • MSUD (available soon)
• Aminoacidurias


  Inborn errors of metabolism that result in excess amino acids or their intermediates in the excreted urine. May result in abnormal urine colors, odors, and crystals.
• Screening test for aminoacidurias

  Ferric chloride tube test
• Aminoacidurias


  • Varying degrees of severity: harmless to conditions which result in early death
  • Most common manifestation: mental retardation
  • CNS dysfunctions: seizures, degenerative disease, or "failure to thrive"
• Classification of aminoacidurias


  • Phenylalanine-Tyrosine Disorders
  • Branched-Chain Amino Acid Disorders
  • Tryptophan Disorders
  • Cystine disorders
• Phenylalanine-Tyrosine Disorders


  Many of the most frequently requested special urinalysis procedures are associated with the phenylalanine-tyrosine metabolic pathway. Major inherited disorders include: PKU, Tyrosyluria, Alkaptonuria, Melanuria.
• Phenylketonuria (PKU)


  Most well known of the aminoacidurias. Occurs in 1 of every 10,000 to 20,000 births. Failure to inherit the gene to produce the enzyme phenylalanine hydroxylase, causing excessive levels of phenylalanine in the blood that will cause brain damage and severe mental retardation.
• Phenylketonuria


  • High levels of phenylketones in the urine, especially phenylpyruvic acid
  • "Musty" or "mousy" urine odor
  • Produces children with fair complexions—even in dark-skinned families
• Patients with PKU appear normal at birth but can become severely afflicted by age 1 if untreated.
• PKU testing


  • MS/MS tests
  • Ferric Chloride Tube Test
  • Guthrie test
• Guthrie test


  1. Blood from a heelstick is absorbed into filter paper circles

  2. Culture media containing beta-2-thienylalanine is streaked with Bacillus subtilis

  3. Blood-impregnated disks are then placed on culture media
• Interpretation of Guthrie test

  Increased phenylalanine = bacterial growth around the paper disks. Phenylalanine counteracts the action of beta-2-thienylalanine, an inhibitor of B. subtilis that is present in the media, and growth will be observed around the paper disks.
• Tyrosyluria


  Urine may contain excess tyrosine or its degradation products, p-hydroxyphenylpyruvicacid and p-hydroxyphenyllactic acid. There are 3 types: Type 1 - deficiency in fumarylacetoacetate hydrolase (FAH), Type 2 - lack of the enzyme tyrosine aminotransferase, Type 3 - lack of the enzyme p-hydroxyphenylpyruvic acid dioxygenase.
• Nitroso-naphthol test for tyrosyluria

  Orange-red color
• Melanuria


  Clinical significance is melanoma. Darkening appears after the urine is exposed to air. These tumors secrete a colorless precursor of melanin, 5,6-dihydroxyindole, which oxidizes to melanogen and then to melanin, producing the characteristic dark urine.
• Screening tests for melanuria

  • Ferric chloride tube test: precipitate
  • Sodium nitroprusside test: red color
• Alkaptonuria


  "Alkali Lover": urine darken after becoming alkaline from standing at room temperature. Darkening is the result of the formation of polymerization products of homogentisic acid.
• Screening tests for alkaptonuria

  • Add alkali to freshly voided urine and observe for darkening of the color
  • Ferric chloride test: transient deep blue color
  • Clinitest: yellow precipitate
• Alkaptonuria


  • Failure to inherit the gene to produce the enzyme homogentisic acid oxidase
  • Homogentisic acid accumulates in the blood, tissues, and urine
  • In later life, brown pigment becomes deposited in the body tissues, particularly noticeable in the ears
  • Deposits in the cartilage eventually lead to arthritis
  • A high percentage of persons with alkaptonuria develop liver and cardiac disorders
• Branched-Chain Amino Acid Disorders

  Two major groups: 1) Accumulation of one or more of the early amino acid degradation products, as seen in maple syrup urine disease. 2) Organic acidemias and result in accumulation of organic acids produced further down in the amino acid metabolic pathway.
• Maple Syrup Urine Disease


  An IEM, inherited as an autosomal recessive trait. Failure to inherit the gene for the enzyme necessary to produce oxidative decarboxylation of the keto acids of leucine, isoleucine, and valine results in their accumulation in the blood and urine.
• Maple Syrup Urine Disease

  • Failure to thrive after approximately 1 week among newborns
  • Urine specimen that produces a strong odor resembling maple syrup
  • Development of severe mental retardation and even death
• Screening test for maple syrup urine disease

  2,4-dinitrophenylhydrazine (DNPH): yellow turbidity or precipitate
• Organic Acidemias


  Include the isovaleric, propionic, and methylmalonic acidemias. Generalized symptoms: early severe illness, often with vomiting accompanied by metabolic acidosis; hypoglycemia; ketonuria; and increased serum ammonia.
• Isovaleric acidemia


  Urine odor of "sweaty feet". Accumulation of isovalerylglycine due to a deficiency of isovaleryl coenzyme A in the leucine pathway.
• Propionic and methylmalonic acidemias


  Result from errors in the metabolic pathway converting isoleucine, valine, threonine, and methionine to succinyl coenzyme A. Propionic acid is the immediate precursor to methylmalonic acid in this pathway.
• Tryptophan disorders


  Metabolites of tryptophan metabolism include indican and 5-Hydroxyindoleacetic acid (5-HIAA).
• 2,4-dinitrophenylhydrazine (DNPH)


  Yellow turbidity or precipitate
• Urine screening test


  Most frequently performed for keto acids
• Procedure


  1. 1 mL urine + 10 drops of 0.2 % 2,4-DNPH in 2N HCl

  2. Wait for 10 minutes