Urine Screening for Metabolic Disorders

Overflow type: Increased amino acids in blood and urine; Examples: PKU, MSUD, cystinosis. Renal type: Normal blood amino acids but increased urine amino acids due to defective tubular reabsorption; Examples: Cystinuria, Fanconi's syndrome.

Failure to inherit a functional gene that codes for a particular enzyme; No gene = No enzyme.

Absence of the gene coding for phenylalanine hydroxylase; Other forms are due to lack of tetrahydrobiopterin; Phenylalanine cannot be converted to tyrosine; Increased phenylpyruvic acid in urine.

Mousy odor of urine, sweat, and breath due to phenylacetic acid; May lead to severe mental retardation.

FeCl₃ tube test: blue-green; Phenistix strip: gray to gray-green; Guthrie bacterial inhibition test; Confirmatory test: Ion-exchange HPLC.

B. subtilis is cultured with β-2-thienylalanine (TE); β-2-TE inhibits B. subtilis growth; Phenylalanine counteracts the inhibition; Positive: bacterial growth; Negative: no growth.

Type 1: Fumarylacetoacetate hydrolase (FAH); Type 2: Tyrosine aminotransferase; Type 3: p-hydroxyphenylpyruvic acid dioxygenase.

May also occur in severe liver disease; Rancid butter odor of urine.

FeCl₃ tube test: transient green; Nitroso-naphthol: orange-red; Confirmatory tests: Chromatography and quantitative serum tyrosine assay.

Blood collection is required 24 hours after birth and before the newborn leaves the hospital; Tandem mass spectrometry (MS/MS) screens infant blood for specific substances associated with inborn errors of metabolism.

Deficiency of homogentisic acid oxidase due to an absent gene; Increased homogentisic acid in blood and urine.

Urine darkens after standing at room temperature and becoming alkaline; Brown or black stains on cloth diapers; Reddish stains on disposable plastic diapers; Homogentisic acid causes black pigmentation of connective tissues and ears (ochronosis).

FeCl₃ tube test: transient blue; Clinitest: yellow precipitate; Alkalinization of fresh urine; Confirmatory tests: Paper/thin-layer chromatography and capillary electrophoresis.

Caused by melanoma, a tumor involving melanocytes; Tumors secrete 5,6-dihydroxyindole, which oxidizes to melanogen and then melanin; Urine darkens upon exposure to air.

Deficient production of melanin.

FeCl₃ tube test: graylack precipitate; Sodium nitroprusside test: red; Ehrlich test: red.

Deficiency of the branched-chain α-keto acid dehydrogenase (BCKD) enzyme complex due to an absent gene; Increased ketoacids of leucine, isoleucine, and valine; Most common inborn error of metabolism in the Philippines.

Caramelized sugar, maple syrup, or curry-like urine odor; Ketonuria in a newborn is significant.

Screening: 2,4-dinitrophenylhydrazine (DNPH), positive yellow turbidity/precipitate; Confirmatory: Gas chromatography or thin-layer chromatography; Nuclear magnetic resonance spectroscopy.

Isovaleric acidemia: sweaty-feet odor due to isovalerylglycine; Glutaric acidemia: may also produce sweaty-feet odor.

Propionic acidemia; Methylmalonic acidemia: p-nitroaniline test, positive emerald-green color.

Indigo-blue urine upon air exposure; Seen in Hartnup disease (blue diaper syndrome) and intestinal disorders.

Obermayer's test: FeCl₃ + urine + chloroform; Positive: violet color.

Tumor of argentaffin or enterochromaffin cells; Produces serotonin, which is carried by platelets and metabolized into 5-HIAA.

FeCl₃ tube test: blue-green; Nitroso-naphthol with nitrous acid: violet.

Bananas, pineapples, tomatoes, avocados, chocolates, walnuts, and plums; These increase serotonin.

Sulfur-like urine odor; Treatment: D-penicillamine.

Renal-type aminoaciduria due to defective tubular reabsorption of cystine, ornithine, lysine, and arginine; Cystine is the only one that crystallizes and is the least soluble.

Brand's modification of Legal's nitroprusside test using cyanide nitroprusside: red-purple; Thin-layer or ion-exchange chromatography; High-voltage electrophoresis.

Overflow-type inborn error of metabolism due to absence of the gene coding for an enzyme responsible for cystine metabolism; Types: nephropathic, intermediate, and ocular cystinosis.

Bone marrow, cornea, lymph nodes, and internal organs.

Defective methionine metabolism leading to increased homocystine; Absence of the gene coding for cystathionine β-synthase.

Silver-nitroprusside test; Positive: red-purple color.

Disorders of porphyrin metabolism.

Red, purple, burgundy-red, purplish-red, or port-wine; Urine may remain colorless in lead poisoning (Harr, Henry).

Red-tinged urine; Negative blood reagent strip; Dietary and medication causes ruled out.

Impaired metabolism of mucopolysaccharides or glycosaminoglycans (proteins + polysaccharides found in connective tissues); Common urinary substances: Dermatan sulfate, keratan sulfate, and heparan sulfate.

Also called gargoylism or MPS Type I; MPS accumulates in the cornea; Skeletal abnormalities and intellectual disability.

Sex-linked recessive; Rarely seen in females; Skeletal abnormalities and intellectual disability.

Mental retardation is the only abnormality.

Acid albumin test: white turbidity; CTAB test: white turbidity; MPS paper test: blue color.

Absence of the gene coding for hypoxanthine-guanine phosphoribosyltransferase (HGPRT); Increased uric acid in blood and urine; Orange sand in diapers.

Glucose strip and positive copper reduction test; Melituria: presence of any sugar in urine.

Inability to metabolize galactose into glucose; Deficiency of galactose-1-phosphate uridyltransferase (GALT), galactokinase, or UDP-galactose-4-epimerase.

Increased galactitol, galactonate, and galactose-1-phosphate; Infant failure to thrive, liver disorders, cataracts, and severe mental retardation.

Glucosuria: Diabetes mellitus; Lactosuria: Pregnancy and lactation; Fructosuria: Parenteral feeding; Pentosuria: Ingestion of large amounts of fruit.

Glomerular disorders; Tubular disorders; Interstitial disorders.

Deposition of immune complexes formed with Group A Streptococcus (S. pyogenes) infection on glomerular membranes; Macroscopic hematuria, proteinuria, dysmorphic RBCs, RBC casts, granular casts, and positive ASO titer.

Deposition of immune complexes from systemic immune disorders (e.g., SLE) on glomerular membranes; Proliferation of epithelial cells inside Bowman's capsule forms crescents; Macroscopic hematuria, proteinuria, and RBC casts.

Deposition of anti-glomerular basement membrane antibody affecting glomerular and alveolar basement membranes; Macroscopic hematuria, proteinuria, and RBC casts.

Anti-neutrophilic cytoplasmic autoantibody (ANCA) binds to neutrophils in vascular walls, causing damage to small vessels in the lungs and glomerulus; p-ANCA forms when neutrophils are fixed in ethanol, while c-ANCA forms when neutrophils are fixed with formalin; Macroscopic hematuria, proteinuria, and RBC casts.

Occurs in children following viral respiratory infections; Decreased platelets disrupt vascular integrity; Macroscopic hematuria, proteinuria, and RBC casts.

Thickening of the glomerular membrane following IgG immune-complex deposition associated with systemic disorders; Microscopic hematuria and proteinuria.

Cellular proliferation affects capillary walls or the glomerular basement membrane, possibly immune-mediated; Glomeruli have visible lobular appearance and a tram-track pattern; Hematuria and proteinuria.

Marked decrease in renal function from glomerular damage precipitated by other renal disorders; Progression to renal failure; Hematuria, proteinuria, glucosuria, cellular and granular casts, and waxy and broad casts.

Deposition of IgA on the glomerular membrane due to increased levels of IgA; Early stages: hematuria; Late stages: findings similar to chronic glomerulonephritis.

Also called nil disease or lipoid nephrosis; Little cellular changes in the glomerulus; Glomeruli appear normal by light microscopy; Electron microscopy reveals loss of podocyte foot processes; Podocyte disruption occurs primarily in children following allergic reactions and immunizations; Associated with HLA-B12; Heavy proteinuria, transient hematuria, and fat droplets.

Disruption of podocytes in certain numbers and areas of the glomeruli while other areas remain normal; IgM and C3 are evident on sclerotic areas using immunofluorescence; Proteinuria and hematuria.

Most common cause of ESRD; Deposition of glycosylated proteins on glomerular basement membranes due to poorly controlled blood glucose levels; Microalbuminuria and positive Micral test.

Genetic disorder showing a laminated and thinning glomerular basement membrane; Findings: See nephrotic syndrome.

Disruption of the electrical charges that produce the tightly fitting podocyte barrier, resulting in massive loss of proteins and lipids; Proteinuria in nephrotic syndrome is greater than 3.5 g/day; Occurs in patients with MCD (children), MGN (adults), FSGS, and MPGN.

Damage to renal tubular cells caused by ischemic or toxic agents; Urine odor: odorless; Microscopic hematuria, proteinuria, RTE cells, RTE casts, hyaline casts, granular casts, waxy casts, and broad casts.

Inherited defect in the production of normal uromodulin by renal tubules, with increased uric acid causing gout; Normal uromodulin is replaced by abnormal forms that destroy RTE cells; Findings: RTE cells and hyperuricemia.

Generalized failure of tubular reabsorption in the proximal convoluted tubule; Glucosuria and possible cystine crystals (amino acid).

Neurogenic DI: Hypothalamus fails to produce ADH; Nephrogenic DI: Renal tubules fail to respond to ADH.

Low specific gravity and polyuria (>15 L/day).

Normal blood glucose with increased urine glucose due to defective tubular reabsorption of glucose; Glucosuria.

Ascending bacterial infection of the urinary bladder; Acute onset of urinary frequency and burning; WBCs and bacteria with no casts, microscopic hematuria, mild proteinuria, and increased pH.

Infection of the renal tubules and interstitium associated with interference of urine flow to the bladder, vesicoureteral reflux, or untreated cystitis; WBCs, bacteria, WBC casts, bacterial casts, and microscopic hematuria.

Recurrent infection of the renal tubules and interstitium due to structural abnormalities affecting urine flow; WBCs, bacteria, WBC casts, bacterial casts, granular casts, waxy casts, broad casts, hematuria, and proteinuria.

Allergic inflammation of the renal interstitium in response to certain medications; Hematuria, proteinuria, increased WBCs (eosinophils >1%), WBC casts, and absence of bacteria.