Chapter 9 Urine screening for Metabolic Disorders

define overflow disorders

so much of metabolite that body can’t metabolize it → gets excreted in urine

define renal disorders

metabolites aren’t getting reabsorbed

Which laboratory test is most useful in the initial screening for many inborn errors of metabolism in newborns?

Newborn tandem mass spectrometry (MS/MS)

how many conditions does Florida Newborn Screening test for?

60 conditions total

• 37 core conditions

• 23 secondary conditions

what causes phenylketonuria (PKU)

failure to inherit the gene that produces phenylalanine hydroxylase

what are the effects of PKU

severe brain damage and mental retardation

• milk has phenylalanine

what are some clinical signs of PKU

• patients may have paler skin and hair

• urine has a mousy or musty odor

A blonde, fair-skinned 8 month old boy presents with abnormal development and a mousy-like odor to his urine. What is the most likely cause? 

Phenylketonuria (PKU)

what are 3 causes of tyrosyluria

1. fumarylacetoacetate hydrolase deficiency (FAH)

2. tyrosine aminotransferase deficiency

3. p-hydroxyphenylpyruvic acid deficiency 

which type of tyrosyluria is the most deadly

type I (FAH)

• liver failure shortly after birth

what is the abnormal substance present in alkpatonuria

homogentisic acid

what are some clinical features of alkaptonuria 

• dark stained diapers with strong odor

• dark spots in white of eyes

• black or blue/black coloration on ears around mouth

• “hunch back” and arthritis

• tendonitis

how may alkpatonuria be suspected via urinanalysis

visible darkening of urine after 12-24 hrs

• caused by absence of homogentisic acid oxidase

what is a cause of melanuria

malignant melanoma

how may melanuria be suspected via urinanalysis

darkening of urine when exposed to air

define maple syrup urine disease

genetic mutation that causes failure to inherit the gene needed for decarboxylation of keto acids → build up of keto acids & toxic byproducts

Maple syrup urine disease results from an inborn error of metabolism of certain types of amino acids. Which ones?

Valine, leucine, isoleucine

what are some clinical symptoms of MSUD

• failure to thrive

• urine has a strong odor of maple syrup (sweet or burnt sugar)

what is the most sensitive marker for MSUD

plasma alloisoleucine level > 5µmol/L

what 2 categories do ketonurias in a newborn fall into

1. accumulation of 1 or more early amino acid degradation products

2. organic acidemias and results in accumulation of organic acids

Hartnup disease

• rare inherited disorder

• mutation of gene that codes for neutral amino acid transporter causes more tryptophan to be converted into indole

• pellagra-like rash and neurological symptoms during “episodes”

• indicanuria → blue diapers

intestinal disorders

• excess tryptophan in intestine is converted into indole

  • could be caused by bacteria (C. diff), obstruction or malabsorption syndromes

The finding of a "blue diaper" is indicative of a defect in the metabolism of

tryptophan

Under normal conditions, tryptophan that is NOT reabsorbed in the intestine is removed from the body as

Indole in the feces

what is the significance of increased urinary 5-hydroxyindoleacetic acid (5-HIAA)?

Carcinoid tumors involving argentaffin cells could cause excess amounts of serotonin

• excretion of 5-HIAA > 25mg/24 hrs

how do you test for 5-HIAA

silver nitroprusside test

define cystinuria

• inherited disorder of tubular reabsorption (autosomal recessive)

  • tubules can’t reabsorb cystine or cannot reabsorb cystine, lysine, arginine, and ornithine

• may form renal calculi

what does a urinalysis of a patient with cystinuria contain

normal urinalysis except for signs of cystine crystals and blood related to passage of crystals

Patients who produce kidney stones at an early age should be tested for the presence of:

cystinuria

define cysinosis

• inborn error of metabolism

• defect in lysosomal membranes prevents release of cystine into cellular cytoplasm for metabolism → cystine crystals in many areas of the body (cornea, bone marrow, lymph nodes, and internal organs)

what does the urinalysis of a patient with cystinosis look like

• low specific gravity

• glycosuria

• phosphaturia

• proteinuria

• NO CRYSTALS

define porphyrias

when there is a breakdown in the synthesis of heme

what are acquired causes of porphyria

• lead poisoning

• excessive EtOH intake

what are some inherited causes of porphyrias

• iron deficiency

• chronic liver disease

• renal disease

what are some signs of acute porphyrias

severe neurovisceral attacks triggered by stress, EtOH, fasting, hormonal changes, and certain medications

• labs show accumulation of porphyrin precursors like aminolevulinic acid (ALA) and porphobilinogen (PBG) which are toxic to the nervous system

what are some signs of cutaneous porphyrias

chronic skin problems due to sun exposure (vampires :0)

what are some symptoms of blistering porphyrias

• sun-exposed skin becomes fragile and prone to blistering, wounds, scarring, thickening, and changes in pigmentation

• sometimes deformities to fingers, nose, and ears occur

what are some symptoms of non-blistering porphyrias

sunlight exposure causes painful burning, itching, and swelling sensations

what does the urinalysis of porphyrias look like

oxidized porphyrins are dark wine-red colored and fluoresce under UV light

what are mucopolysaccharides

a group of large compounds in connective tissue that consist of a protein core with numerous polysaccharide branches

what are the 3 most common incompletely metabolized polysaccharide portions are most frequently found in the urine of patients with mucopolysaccharide disorders?

1. dermatan sulfate

2. keratan sulfate

3. heparan sulfate

what are the 3 syndromes of mucopolysaccharide disorders?

1. Hurler syndrome

2. Hunter syndrome

3. Sanfilippo syndrome

define Lesch-Nyhan disease

•Disorder of purine metabolism

•Inherited as sex-linked recessive

•Failure to inherit the gene that produces enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT)

•results in massive excretion of urinary uric acid crystals.

what are some clinical presentation of Lesch-Nyhan disease

•Severe motor defects

•Intellectual disability

•Tendency toward self-destruction

•Gout

•Renal calculi

The presence of "orange sand" in an infant's diaper is indicative of

Lesch-Nyhan disease

what condition is associated with the presence of uric acid in serum

gout

galactosemia

inborn error of carbohydrate metabolism