CHAPTER 9: UA FOR METABOLIC DISORDERS Flashcards
These are amino acid disorders (9)
- Phenylketonuria (PKU)
- Tyrosyluria
- Melanuria
- Alkaptonuria
- Maple syrup urine disease (MSUD)
- Organic acidemias
- Indicanuria
- Cystinosis
Overflow inherited disorders
- Phenylketonuria
- Tyrosinemia
- Alkaptonuria
- Maple syrup urine disease
- Organic acidemias
- Cystinosis
- Porphyria
- Mucopolysaccharidoses
- Galactosemia
- Lesch-Nyhan disease
Metabolic disorders
- Infantile tyrosinemia
- Melanuria
- Indicanuria
- 5-Hydroxyindoleacetic acid
- Porphyria
Renal disorders
- Hartnup disease
- Cystinuria
Results from disruption of
a normal metabolic pathway
Overflow disorders
Causes increased plasma
concentration of the non-metabolized substances.
Overflow disorders
Failure to inherit gene to produce a particular enzyme
Inborn Error of Metabolism (IEM)
Capable of screening the infant blood sample for specific substances associated with particular IEMs
Tandem mass spectrophotometry (MS/MS)
Major inherited disorders (Phenylalanine-Tyrosine Disorders)
- PKU
- Alkaptonuria
- Tyrosyluria
Most well-known of the aminoacidurias. Occurs in 1 OF EVERY 10,000 TO 20,000 BIRTHS and undetected, can lead to severe mental retardation
Phenylketonuria (PKU)
Phenylketonuria (PKU) is identified by?
Ivan Folling (1934) in Norway
Mentally retarded children’s urine:
Mousy odor
PKU is caused by failure to inherit gene to produce enzyme:
phenylalanine hydroxylase
Analysis of urine in PKU
Increase amount of keto acids (phenylpyruvate)
If the cut-off level for normal results is lowered from ______ to ______, the presence of PKU should be detected
4mg/dl; 2mg/dl
Phenylalanine can be detected as early as?
4 hours after birth
This is used in urine testing as follow-up test to ensure proper dietary control
Ferric Chloride
FERRIC CHLORIDE + URINE WITH
PHENYLPYRUVIC ACID =
permanent BLUE GREEN COLOR
Excess tyrosine in plasma
Tyrosinemia
Disorder of Tyrosine Metabolism can either be?
Inherited or Metabolic defects
Tyrosine degradation products:
- p-hydroxyphenylpyruvic acid
- p-hydroxyphenyllactic acid
Frequently seen in pre-mature infants and is caused by underdevelopment of liver function
Tyrosinemia
Produces tyrosyluria resembling transitory newborn screening variety & more serious conditions.
Acquired severe liver disease
Hereditary disorder in which enzymes required in metabolic pathway are not produced
Aminoaciduria
Hereditary disorders are classified into several types producing:
- Tyrosylemia
- Tyrosyluria
Caused by the enzyme fumarylacetoacetate hydrolase (FAH)
Type 1 Tyrosinemia
Produces a generalized renal tubular disorder and progressive liver failure in infants soon after birth.
Diagnosed by the detection of tyrosine and succinylacetone in the urine and blood.
Type 1 Tyrosinemia
Caused by the lack of the enzyme tyrosine aminotransferase.
People with this condition develop corneal erosions and lesions on the palms, fingers, and soles of the feet, believed to be caused by crystallization of tyrosine in the cells.
Type 2 tyrosinemia
This is used as a screening test for Tyrosinemia types 1, 2, and 3
MS/MS
Caused by lack of the enzyme
p-hydroxyphenylpyruvic acid dioxygenase.
Type 3 tyrosinemia
This can result in intellectual disability, seizures, and intermittent ataxia if dietary restrictions of phenylalanine and tyrosine are not implemented
Type 3 tyrosinemia
In Nitroso-Naphtol Test for tyrosine what color produced should be observed?
Orange-red **which indicate Tyrosine metabolite
Pigment responsible for the dark color of hair, skin, and eyes
Melanin
Deficient production of melanin
Albinism
Causes the darkening that appears after urine is exposed to air
Urinary melanin
This is a serious finding that indicates proliferation of the normal melanin-producing cells (melanocytes), producing a malignant melanoma
Elevated Urinary Melanin
Produces 5,6,-hydorxyindole that will oxidize melanogen to melanin.
Malignant Myeloma
One of the six original inborn errors of metabolism described by Garrod in 1902
Alkaptonuria
Urine from patients with this condition darkened after becoming alkaline from standing at room temperature
Alkaptonuria
3rd major aminoacidura
Alkaptonuria
Used for Quantitating Homogentisic Acid.
Gas chromatography–mass spectrometry (GC-MS)
Alkaptonuria results because of failure to inherit the gene to produce the enzyme
homogentisic acid oxidase
Two Major Groups of Branched-Chain Amino Acid Disorders:
- Maple Syrup Urine Disease (MSUD)
- Organic Acidemia
Accumulation of one or more of the early amino acid degradation products
Maple Syrup Urine Disease (MSUD)
Accumulation of organic acids produced further down in the amino acid metabolic pathway
Organic Acidemia
This differs from other amino acids by having METHYL
GROUP
Branched-Chain Amino Acid
This is also included in newborn screening using MS/MS. Caused by IEM, inherited an autosomal recessive trait.
Maple Syrup Urine Disease (MSUD)
Amino acids involved in Maple Syrup Urine Disease (MSUD)
LIV
1. Leucine
2. Isoleucine
3. Valine
Reacts in several of the routinely used screening tests for metabolic disorders.
Homogentisic acid
Homogentisic acid reacts to ferric chloride test by producing?
deep blue color
Homogentisic acid reacts to Clinitest by producing?
Yellow precipitate indicates the presence of a reducing substance
Another screening test for urinary homogentisic acid is to add ______to freshly voided urine and observed for darkening of the color.
However, large amounts of _________ interfere with this reaction
alkali; ascorbic acid
Ketunoria in newborn
Branched-Chain Amino Acid Disorder
Deficiency in decarboxylases and transaminases
Maple Syrup Urine Disease (MSUD)
3 Common encountered acidemias:
- Isovaleric Acidemia
- Propionic Acidemia
- Methylmalonic Acidemia
detected by newborn screening program using MS/MS
Possess a characteristic odor of sweaty feet. Caused by the accumulation of isovalerylglycine and eficiency in isovaleryl coenzyme
Isovaleric Acidemia
Result from errors in the metabolic pathway converting isoleucine, valine, threonine, and
methionine to succinyl coenzyme A
Propionic and Methylmalonic Acidemia
Immediate precursor to methylmalonic acid
Propionic acid
increased amounts of tryptophan are converted to indole and then to indican then eventually excreted in urine
Indicanuria
Seen in malabsorption, obstruction, and in** rare inherited disorder (Hartnup’s disease.)**
Indicanuria
Caused by excessive production of SEROTONIN, which results to elevated urinary 5-HIAA
5-Hydroxyindoleacetic Acid
Metabolism of tryptophan is the increase urinary excretion of metabolites:
Indicant and 5-Hydroxyindoleacetic Acid (5-HIAA)
Normal daily excretion of 5-HIAA is
2-8 mg/ day.
In 5-HIAA, increased production is seen in?
argentaffinoma (>25 mg/day)
Defect in the renal transport of amino acid and is characterized by marked by elevated amounts of the amino acid cystine in the urine
Cystinuria
Sulfur odor of urine sample
Cystinuria
Regarded as a genuine Inborn Error of Metabolism
Cystinosis
Presence of crystalline deposits of cystine crystals in different areas of the body (eyes, BM, lymph nodes)
Fanconi’s syndrome also occurs.
Cystinosis
Due to the defect in methionine metabolism.
Homocystinuria
Increased in this can result in failure to thrive, cataracts, mental retardation, thromboembolic problems, and death
homocystine
intermediate compounds in the production of heme
Porphyrin
A common disease of early royalty in Europe as a result of intermarriage among the royals of different countries.
Porphyria
Disorders of porphyrin metabolism. Can be inherited or acquired from erythrocytic and
hepatic malfunctions or exposure to toxic agents.
Porphyria
Skeletal structure is abnormal. There is severe mental retardation.
Hurler’s Syndrome
Products most frequently found in the urine are dermatan sulfate, keratan sulfate, and heparan sulfate
Mucopolysaccharide
Accumulation of mucopolysaccharide in the cornea of the eye
Hurler’s Syndrome
Can cause mental retardation ONLY!
Sanfilippo’s Syndrome
An inherited disorder that is characterized by massive excretion of urinary URIC ACID Crystals
Lesch-Nyhan Disease
Deficiency in hypoxanthine-guanine phosphoribosyl transferase.
Lesch-Nyhan Disease
Patients suffer from severe motor defects, mental retardation tendency toward self- destruction, gout, and renal calculi
Lesch-Nyhan Disease
A general term pertaining to increased urinary sugar. Inherited in nature and does not cause any disturbance in the body’s metabolism.
Melituria
The presence of galactose in urine is due to the inability of the body to metabolize galactose to glucose
Galactosuria
Galactosuria can be caused by the deficiency in any of the three
enzymes:
- Galactose-1-phosphate uridyl transferase (GALT)
- Galactokinase
- UDP-galactose-4-epimerase
Can cause the most severe and fatal symptoms associated with galactosuria
Galactose-1-phosphate uridyl transferase (GALT)
Deficiency can cause cataract development in adulthood
Galactokinase
May be asymptomatic or can produce mild melaturic
symptoms.
UDP-galactose-4-epimerase
Other causes of Melituria
Lactosuria and Fructosuria
Associated with parenteral feeding and pentosuria with ingestion of large amounts of fruit.
Fructosuria
May be seen during pregnancy and lactation.
Lactosuria
