Urine Screening for Metabolic Disorders

Overflow

Breakdown in a normal metabolic pathway causing accumulation of previous metabolite.

Overflow

Inherited lack of specific enzyme for protein, fat, or carbohydrate metabolism - Inborn Error of Metabolism.

Renal

Functional defects

Phenylketonuria

1 in 10,000 births. Autosomal-recessive; heterozygotes normal.

Phenylketonuria

Eliminate phenylalanine from diet (milk). Damage to child's mental capacity.

Phenylketonuria

Alternate pathways as child matures. Avoid high phenylalanine foods (aspartame).

Green-Blue

Urine and 5% ferric chloride produces a permanent _______.

Guthrie Blood Test

Media containing beta-2-thienylalanine, an inhibitor of Bacillus subtilis, is streaked with the bacteria; blood-impregnated discs placed on the agar; phenylalanine counteracts the inhibitor, and bacteria grow around the disc.

Tyrosyluria/Tyrosinemia

Premature transient tyrosinemia, underdevelopment of liver function, and acquired severe liver disease.

Type 1 Tyrosyluria/Tyrosinemia

Enzyme deficient is Fumarylacetoacetate hydrolase (FAH).

Type 1 Tyrosyluria/Tyrosinemia

Produces a generalized renal tubular disorder and progressive liver failure in infants soon after birth.

Type 2 Tyrosyluria/Tyrosinemia

Enzyme deficient is tyrosine aminotransferase.

Type 2 Tyrosyluria/Tyrosinemia

Persons develop corneal erosion and lesion on the palms, fingers, and soles of the feet believed to be caused by crystallization of tyrosine in the cells.

Type 3 Tyrosyluria/Tyrosinemia

Enzyme deficient is p-hydroxyphenylpyruvic acid dioxygenase.

Type 3 Tyrosyluria/Tyrosinemia

Result in mental retardation if dietary restrictions of phenylalanine and tyrosine are not implemented.

Ferric Chloride

In urine test for tyrosyluria/tyrosinemia, it produces a transient green color- do not confuse with phenylalanine.

Nitroso-naphthol

In urine test for tyrosyluria/tyrosinemia, it produces an orange-red color.

Melanuria

Second pathway for tyrosine.

Melanin

Pigment for dark hair, skin. Defect causes albinism.

Malignant Melanoma

Increased production of melanin results in ________>

Melanuria

Dark urine from oxidation of melanogen.

Melanin

Black precipitate with ferric chloride. Red color with sodium nitroprusside.

Ferric Chloride Tube Test

Test for melanuria; oxidation of chromogen.

Red Color

Color produced in screening test of sodium nitroprusside test for melanuria.

Sodium Nitroprusside Test

Interference -> add glacial acetic acid (reverts color greenish-black).

Purple

In sodium nitroprusside test, acetone turns into color ______.

Amber

In sodium nitroprusside test, creatinine turns into color _____.

Alkaptonuria

Enzyme deficiency is homogentisic acid oxidase.

Alkaptonuria

Black alkaline urine, possible black-staine diapers.

Alkaptonuria

Manifests later in life with brown pigment deposits in tissues.

Alkaptonuria

Urine: blue with ferric chloride, yellow precipitate with Clinitest, black with silver nitrate and ammonium hydroxide; quantitative tests available.

FeCl3 Test

Homogentisic acid test that is the screening test for metabolic disorder.

FeCl3 Test

In Homogentisic acid test its result is transient deep blue color in test tube.

Clinitest

In Homogentisic acid test, it is a test for reducing substance.

Clinitest

In Homogentisic acid test, its result is yellow precipitate.

Urinary Homogentisic Acid Test

In Homogentisic acid test, it is a screening test. Add alkali to freshly voided urine.

Urinary Homogentisic Acid

In Homogentisic acid test, observe for darkening of the color (ascorbic acid interferes the test).

Ammoniacal Silver Nitrate Test

In Homogentisic acid test, addition of silver nitrate and ammonium hydroxide to urine.

Ammoniacal Silver Nitrate Test

In Homogentisic acid test, it results in black urine.

Branched Chain Amino Acid Disorders

Amino acids with a methyl group.

Maple Syrup Urine Disease (MSUD)

Group in branched chain amino acid disorders where in early degradation products accumulate.

Organic Acidemias

Group in branched chain amino acid disorders where in accumulation of organic acids further down in pathway.

Maple Syrup Urine Disease (MSUD)

Inborn error of metabolism, autosomal recessive. 1 week failure to thrive is noticed.

Maple Syrup Urine Disease (MSUD)

Urine: strong odor of maple syrup, and thick, dark appearance.

Maple Syrup Urine Disease (MSUD)

Dietary regulation. Screening test 2,4-dinitrophenylhydrazine produces yellow precipitate turbidity. Positive urine ketones.

Isovaleric Acidemia

In organic acidemias, it has a sweaty feet odor of urine.

Isovaleric Acidemia

In organic acidemias, there is accumulation of isovalerylglycine.

Isovaleric Acidemia

In organic acidemias, it causes isovaleryl coenzyme. A deficiency in the leucine pathway.

MS/MS

Test method for isovaleric acidemia.

Propionic Acidemia

In organic acidemias, it has immediate precursor to methylmalonic acid.

Propionic Acidemia and Methylmalonic Acidemia

In organic acidemias, it has errors in the metabolic pathway converting isoleucine, valine, threonine, and methionine to succinyl coenzyme A.

p-Nitroaniline Urine Test (Emerald Green)

Test method for methylmalonic acidemia.

Indicanuria

Tryptophan enters intestine; is reabsorbed or is converted to indole by bacteria and leaves in the feces.

Indicanuria

Intestinal disorders and Hartnup disease cause increased tryptophane conversion to indole.

Hartnup Disease

Blue diaper syndrome.

Indicanuria

Increased indole reabsorbed, excreted by kidney on its way to the liver.

Indigo Blue

Exposure of urine to air.

Cystinuria

Inherited cystine disorder affecting renal reabsorption.

Red-Purple Color

In cyanide-nitroprusside test, observe for _____.

Cystinuria

Elevated amino acid cystine in urine (+) cystine crystals in urine.

Cystinuria

Caused by inability of the renal tubules to reabsorb cystine filtered by the glomerulus.

Cystinuria

Test and result is cyanide-nitroprusside test (red-purple color)>

Cystinosis

Crystalline deposits of cystine in many areas of the body.

Cystinosis

Caused by defect in the lysosomal membranes.

Cystinosis

It has positive test results for reducing substances.

Homocystinuria

Increase in homocystine throughout the body.

Homocystinuria

Causes defect in methionine metabolism.

Homocystinuria

Test and result are (+) cyanide-nitroprusside test plus (+) silver-nitroprusside test.

Feces/Bile

In porphyrin disorders, coproporphyrine and protoporphyrine is seen in ______.

Urine

In porphyrin disorders, ALA, porphobilinogen, and urobilinogen is present in here.

Blood

In porphyrin disorders, free erythrocyte production for lead poisoning is seen in ______.

Porphyrin Disorders

Urine: port wine color after air exposure, also seen on diapers.

Hurler Syndrome and Hunter Syndrome

In mucopolysaccharide disorders, skeletal structure is abnormal and there is severe mental retardation.

Hurler Syndrome

In mucopolysaccharide disorders, mucopolysaccharides accumulate in the cornea of the eye.

Sanfilippo Syndrome

In mucopolysaccharide disorders, it has mental retardation.

Blue Color

For mucopolysaccharide paper test, observe for ______.

Purine Disorder (Lesch-Nyhan Disease)

It is caused by failure to inherit the gene to produce the enzyme hypoxanthine guanine phosphoribosyl-transferase.

Pentosuria

In carbohydrate disorder, one of Garrod's original six IEMs.

Galactosuria

Deficiency in any of three enzymes, galactose-1-phosphate uridyl transferase (GALT), galactokinase, and UDP-galactose-4-epimerase.

Lactosuria

In carbohydrate disorder, it is seen during pregnancy and lactation.

Fructosuria

In carbohydrate disorder, parental feeding and ingestion of large amounts of fruit.

Red Precipitate

For fructose screening test, observe for a _____.