Metabolic Disorders Urine

Overflow Disorders

Disruption of a normal metabolic pathway that causes increased plasma concentrations of non-metabolized subtances

Renal Type

Abnormal accumulations are caused by malfunctions in the tubular reabsorption mechanism

a

Overflow type aminoaciduria: 1. ↑ A.A in blood 2. Normal A.A in blood 3. ↑ A.A in Urine 4. ↓ A.A in urine

a. 1, 3
b. 1, 4
c. 2, 3
d. 2, 4

c

Renal type aminoaciduria: 1. ↑ A.A in blood 2. Normal A.A in blood 3. ↑ A.A in Urine 4. ↓ A.A in urine

a. 1, 3
b. 1, 4
c. 2, 3
d. 2, 4

9288

Newborn Screening Act aka RA?

Tandem Mass Spectrophotometry (MS/MS)

What is the method recommended to detect IEM?

Congenital Hyperthyroidism, Congenital Adrenal Hyperplasia, Galactosemia, Phenylketonuria, Glucose-6-Phosphate-Dehydrogenase Deficiency, Maple Syrup Urine Disease

Disorders Tested for Newborn Screening (6)

PKU, Tyrosyluria, Alkaptonuria, Melanuria

Enumerate the Phenylalanine-Tyrosine Disorders

Phenylalanine hydroxylase

Phenylketonuria (PKU) is a failure to inherit the gene that produces what enzyme? (autosomal recessive)

Mousy odor

Odor of urine in people with Phenylketonuria

Phenylalanine (milk, dairy)

In people diagnosed with Phenylketonuria, foods rich in what are avoided?

Robert Guthrie Bacterial Inhibition Test

A screening test for Phenylketonuria that utilizes B. subtilis

Newborn Screening Reference Center

Disorders Tested for Newborn Screening follows the standard set by?

Homogentisic acid oxidase

Enzyme deficient in Alkaptonuria

2-6 weeks

Urinary accumulation in Phenylketonuria takes how long?

Bacillus subtilis

Robert Guthrie Bacterial Inhibition Test make use of what bacteria

FeCl3 tube test, Phenistix strip, Guthrie bacterial inhibition test

Screening tests for Phenylketonuria

blue-green

color of a positive FeCl3 tube test for PKU

gray to gray-green

color of a positive Phenistix strip for PKU

(+) PKU

Upon performing the Guthrie Bacterial Inhibition test you have noticed growth, what can you conclude?

HPLC

Considered as the confirmatory test for PKU

NIH

Confirmatory Lab for PKU

d

Clinical Presentation of PKU:
a. Ochronosis, tendonitis, and presenting dark colored urine upon standing at room temperature
b. No melanin pigment for producing dark color in the hair, skin and eyes
c. Lesions on palms and soles of feet and corneal erosion
d. Fair complexion despite coming from families that are dark-skinned due to decreased Tyrosine production and melanin content

b

Tylosuria is a deficiency in tyrosine or degradation products such as:
1. p-hydroxyphenylpyruvic acid
2. fumarylacetoacetic acid hydrolase
3. p-hydroxyphenyllactic acid
4. maleylacetoacetic acid isomerase

a. 1,2,3
b. 1,3
c. 2,4
d. 4

a

Enzyme deficient in Tyrosinemia (Tylosuria) type 1 (Tyrosinosis)

a. Fumarylacetoacetic acid hydrolase
b. Tyrosine aminotransferase
c. Maleylacetoacetic acid isomerase
d. p-hydroxyphenylpyruvate oxidase

c

Enzyme deficient in Tyrosinemia (Tylosuria) type 1B

a. Fumarylacetoacetic acid hydrolase
b. Tyrosine aminotransferase
c. Maleylacetoacetic acid isomerase
d. p-hydroxyphenylpyruvate oxidase

b

Enzyme deficient in Tyrosinemia (Tylosuria) type 2 (Richner-Hanhart syndrome)

a. Fumarylacetoacetic acid hydrolase
b. Tyrosine aminotransferase
c. Maleylacetoacetic acid isomerase
d. p-hydroxyphenylpyruvate oxidase

d

Enzyme deficient in Tyrosinemia (Tylosuria) type 3

a. Fumarylacetoacetic acid hydrolase
b. Tyrosine aminotransferase
c. Maleylacetoacetic acid isomerase
d. p-hydroxyphenylpyruvate oxidase

a

Generalized renal tubular disorder
Progressive liver failure:

a. Type 1 (Tyrosinosis)
b. Type 3
c. Type 2 (Richner-Hanhart syndrome)
d. Type 4

c

Produce lesions on palms and soles of feet
Due to crystallization of tyrosine in the cells

a. Type 1 (Tyrosinosis)
b. Type 3
c. Type 2 (Richner-Hanhart syndrome)
d. Type 4

b

Tyrosyluria type:
If not treated, could lead to mental retardation

a. Type 1 (Tyrosinosis)
b. Type 3
c. Type 2 (Richner-Hanhart syndrome)
d. Type 4

Rancid butter

Urine odor of people with Tyrosinemia/Tyrosyluria

orange-red

A positive color for the Nitroso-napthol test for tyrosyluria:

Melanuria

Overproliferation of the normal melanin-producing cells (melanocytes) producing malignant melanoma
Increased urinary melanin produces darkening of urine when exposed to air

5,6-dihydroxyindole

This is secreted by a tumor in people with melanuria

melanogen to melanin

tumor secretion in melanuria oxidizes?

air exposure

In people with melanuria urine darkens upon

Albinism

Deficient production of melanin
No melanin pigment for producing dark color in the hair, skin and eyes

Alkaptonuria

Absence of Hemogentisic acid oxidase

alkaline

In people with Alkpatonuria urine darkens after becoming

Brown-stained or black-stained

Color of cloth diapers in babies with Alkaptonuria

Reddish-stained

Color of disposable diapers in babies with Alkaptonuria

Ochronosis

deposition of black pigment in skin, ct, and cartilage of ppl with alkaptonuria

Branched-chain Amino Acid Disorders

Refers to amino acids that have a Methyl group attached that branches from the main aliphatic carbon chain;
Presence of ketonuria in newborns

MSUD, Organic Acidemias

Enumerate the Branched\=chain amino acid Disorders

Maple Syrup Urine Disease (MSUD)

Failure to inherit the gene for enzyme necessary to produce oxidative decarboxylation of ketoacids in metabolic pathways of Leucine, Isoleucine, Valine

Leucine, Isoleucine, Valine

MSUD is failure to inherit the genes to oxidize what amino acids?

Caramelized sugar/maple syrup/curry

MSUD will produce what type of urine odor?

2,4-dinitrophenylhydrazine (DNPH)

Screening test to detect MSUD

yellow turbidity or precipitate

2,4-dinitrophenylhydrazine (DNPH) screening test for MSUD produces what color for a positive result

Gas or TLC, Nuclear magnetic resonance spectro

Confirmatory test to detect MSUD

Organic Acidemias

Accumulation of organic acids produced further down in the amino acid metabolic pathway

Isovaleric Acidemia

Sweaty-feet odor
Accumulation of isovalerylglycine (isovaleryl coenzyme A deficiency)

isovaleryl coenzyme A deficiency

Isovaleric acidemia is an accumulation of isovalerylglycine due to the absence of?

Propionic and Methylmalonic Acidemia

Error in metabolic pathway of Isoleucine, Valine, Threonine, Methionine which converts to succinyl coenzyme A

p-nitroaniline test

Test for Isovaleric acidemia that imparts a Emerald-green color

Indicanuria, Argentaffinoma

Enumerate the Tryptophan Disorders

Indicanuria

Caused by obstruction, presence of abnormal bacteria, malabsorption, Hartnup disease

Obermayer's test

Screening test for Indicanuria

Blue-diaper syndrome

Production of blue color indican that is oxidized upon exposure to air

violet

A positive color for Obermayer's test for indicanuria

Fanconi syndrome

If indicanuria is not treated properly it can further progress to?

5-Hydroxyindoleacetic acid (5-HIAA)

Degradation product of Serotonin used in the stimulation of smooth muscles

2-8 mg/24 hrs

Normal levels of 5-HIAA

25 mg/24 hrs

Argentaffin cell tumor levels of 5-HIAA

Argentaffin cell tumor

Carcinoid neuroendocrine slow-growing tumor found in the rectal colon
Tends to produce excess 5-HIAA

bananas, pineapples, tomatoes

In testing for Argentaffinoma patients must not eat

Cystinuria, Cystinosis

Enumerate the Cystine Disorders

Sulfur odor

Odor of the urine with people with Cystine Disorders

Cystinuria

Defect in the tubular transport of amino acids
Defective reabsorption of: Cystine, Arginine, Lysine, Ornithine or Cystine and Lysine only

Cystine
Ornithine
Lysine
Arginine

Cystinuria is the defective reabsorption of what A.A?

Cystinosis

Incomplete metabolism of cystine results in crystalline deposits of cystine in many areas of the body including:
Cornea
Bone marrow
Lymph nodes
Internal organs

Homocystinuria

Defect in the metabolism of methionine which produces an increase in homocystine

cystathionine B-synthase

Homocystinuria is the Deficiency of what liver enzyme

Porphyrias

Can be inherited or acquired from erythrocytic & hepatic malfunctions or exposure to toxic agents (Lead poisoning)

Red or Port wine color urine

Porphyrinuria urine color

colorless

Acquired porphyria due to lead poisoning urine color

Red (red diaper syndrome)

Color of infants diaper in porphyria

Free erythrocyte protoporphyrin (FEP)

CDC recommended test for lead poisoning

Mucopolysaccharide Disorders

Deficiencies of enzymes involved in degradation of glycosaminoglycans (mucopolysaccharides)

Hurler, Hunter, Sanfiippo

Enumerate the Mucopolysaccharide disorders

Hurler

type of Mucopolysaccharide disorder that causes MPS to accumulate in the cornea of the eye

Hunter

type of Mucopolysaccharide disorder that is sex-linked recessive and is rarely seen in females

Sanfilippo

Type of MPS disorder where mental retardation is the only abnormality

Acid-albumin, cetyltrimethylammonium bromide (CTAB), MPS paper test

Screening tests for MPS disorders

(+) white turbidity

Acid albumin positive result for MPS

(+) white turbidity

CTAB test positive result for MPS

(+) blue color

MPS paper test positive result for MPS

Dermatan sulfate, Keratan sulfate, Heparan sulfate

Products in the urine due to Mucopolysaccharide Disorders

Lesch-Nyhan Disease

Failure to inherit the gene to produce the enzyme hypoxanthine guanine phosphoribosyltransferase