Screeng For Metabolic Disorders: Phenylalanine-Tyrosine disorders

Question 1

result from disruption of a normal metabolic pathway that causes **increased plasma concentrations of the nonmetabolized substances. **

These chemicals either override the reabsorption ability of the renal tubules or are not normally reabsorbed from the filtrate because they are present in only minute amounts.

Abnormal accumulations of the renal type are caused by malfunctions in the tubular reab-sorption mechanism

Answer 1

Overflow disorders

Question 2

Disruption of enzyme function can be caused by failure to inherit the gene to produce a particular enzyme, referred to as an_________, or by ______n from disease or toxic reactions.

Answer 2

inborn error of metabolism (IEM)

organ malfunctio

Question 3

Testing for many substances is now performed using________.

It is capable of screening the infant blood specimen for specific substances associated with particular IEMs.

Methods for specific gene testing also are being developed rapidly.

Answer 3

tandem mass spectrophotometry (MS/MS)

Question 4

Amino Acid Disorders
The amino acid disorders with urinary screening tests include (9)

PTMAM O ICC

Answer 4

phenylketonuria (PKU)
tyrosyluria
melanuria
alkaptonuria
maple syrup urine disease (MSUD)
organic acidemias
indicanuria
cystinuria
cystinosis

Question 5

Major inherited disorders include.

Metabolic defects cause overproduction of melanin.

Answer 5

PKU, tyrosyluria, and alkaptonuria
Phenylalanine-Tyrosine Disorders

Question 6

• Metabolic disturbances that produce substances involved in protein, fat, and carbohydrate metabolism

• Vast number of involved enzymes

Answer 6

OVERFLOW DISORDERS

Question 7

• Main cause: disruption of enzyme function
• Failure to inherit the gene that produces the enzyme
• Organ malfunction from disease or toxic reactions

Answer 7

OVERFLOW DISORDERS

Question 8

• Traditionally performed to detect and monitor newborns for any inborn error of metabolism
•_____ tests performed in the expanded newborn screening (before: 6)

Answer 8

NEWBORN SCREENING TESTS

29

Question 9

METABOLIC DISORDERS

Answer 9

• AMINO ACID DISORDERS
• PORPHYRIN DISORDERS
• MUCOPOLYSACCHARIDE DISORDERS
• PURINE DISORDERS
• CARBODHYRATE DISORDERS

Question 10

Phenylalanine-Tyrosine disorders

PMAT

Answer 10

• Phenylketonuria
• Melanuria
• Alkaptonuria
• Tyrosyluria

Question 11

• Branched-chain amino acid disorders

Answer 11

• MSUD
• Organic acidemias

Question 12

• Tryptophan disorders

Answer 12

• Indicanuria
• 5-hydroxyindoleacetic acid

Question 13

• Cystine disorders

Answer 13

• Cystinuria
• Cystinosis
• Homocystinuria

Question 14

PHENYLKETONURIA

• The most important and sometimes the only manifestation of PKU is______
• accumulation of phenylalanine, phenylpyruvic acid, and other acid metabolites interfere with____ and other neurologic functions
•______ odor in urine may be detected
• Management: avoidance of food rich in_______

Answer 14

mental retardation
myelination
Mousy
phenylalanine

Question 15

PHENYLKETONURIA
• Increased phenylalanine levels due to defective or absent_____

• Phenylalanine is converted instead into _______which may also be detected

Answer 15

phenylalanine hydroxylase

phenylpyruvic acid

Question 16

URINE TEST FOR PHENYLKETONURIA
•_________

Answer 16

Ferric chloride tube test

Question 17

Ferric chloride acid test for PKU

• Detects _______
• 5 drops of______ to 1 mL of____
• A permanent_____ color is positive

Answer 17

phenylpyruvic acid

10% ferric chloride; urine

blue-green

Question 18

• Accumulation of excess tyrosine in the plasma (tyrosinemia) produces urinary overflow

Answer 18

TYROSYLURIA

Question 19

TYROSYLURIA

p-hydroxyphenylpyruvic acid dioxygenase

Answer 19

• Tyrosinemia type 3:

Question 20

TYROSYLURIA

tyrosine aminotransferase

Answer 20

• Tyrosinemia type 2:

Question 21

TYROSYLURIA

fumarylacetate hydrolase

Answer 21

• Tyrosinemia Type 1 :

Question 22

• Results into mental retardation if dietary restrictions of phenylalanine and tyrosine are not implemented

Answer 22

Tyrosyluria

Question 23

URINE TEST FOR TYROSYLURIA

Answer 23

Nitroso-naphthol test

Question 24

URINE TEST FOR TYROSYLURIA
• Nitroso-naphthol test

• 5 drops of____ + 1 mL of_____ + 1 drop of_____ + 0.1 mL_____

• Mix and wait for 5 minutes

•_______ color indicates presence of tyrosine metabolites

Answer 24

urine;
2.63 N nitric acid;
21.5% sodium nitrite;
nitroso-2-naphthol

Orange-red

Question 25

MELANURIA •________: product of a second metabolic pathway for tyrosine • Deficient production of melanin results in______ • Increased levels of melanin:____

Answer 25

Melanin albinism melanuria

Question 26

MELANURIA • Proliferation of______ which produces melanoma • Cancer cells produce_____ which oxidizes to melanogen and then to melanin

Answer 26

melanocytes 5,6-dihydroxyindole

Question 27

Urine darkens upon exposure to air

Answer 27

MELANURIA

Question 28

ALKAPTONURIA • Failure to inherit the gene that codes for the enzyme_______

Answer 28

homogentisic acid oxidase

Question 29

• Urine darkens/turns to black upon standing

Answer 29

LAKAPTONURIA

Question 30

• Accumulation of homogentisic acid in blood, tissues, and urine

Answer 30

ALKAPTONURIA

Question 31

• ***Brown-stained or black-stained or red-stained diapers*** • Deposition of brown pigment in body tissues like the ears ***(ochronosis)*** • ***Deposits in the cartilage*** cause arthritis • No developmental delays or cognitive issues; only ***chronic pain and mobility problems***

Answer 31

ALKALTONURIA

Question 32

URINE TESTS FOR ALKAPTONURIA

Answer 32

• Ferric chloride test • Clinitest • Homogentisic acid test

Question 33

URINE TESTS FOR ALKAPTONURIA • Ferric chloride test:_____ • Clinitest:_____ • Homogentisic acid test:____

Answer 33

deep blue color yellow precipitate Observe for black color

Question 34

PKU • Treatment:

Answer 34

• Dietary control to limit phenylalanine (found in milk). • Avoid products containing aspartame (found in diet foods, sodas, etc.).

Question 35

PKU Screening Timing: • Blood collection should happen_____ after birth. • Early release of newborns may affect detection; PKU may be detectable as early as _____after birth.

Answer 35

24–48 hours 4 hours

Question 36

Types of Hereditary Tyrosinemia: • Leads to renal tubular disorder and progressive liver failure. • Diagnosis: Tyrosine and succinylacetone in urine/blood, genetic testing.

Answer 36

Type 1

Question 37

Types of Hereditary Tyrosinemia: Symptoms: Corneal erosions and lesions on palms, fingers, and soles of feet. Diagnosis: Elevated plasma tyrosine and 4-hydroxyphenylpyruvic acid in urine.

Answer 37

Type 2

Question 38

Types of Hereditary Tyrosinemia: • Symptoms: Intellectual disability, seizures, intermittent ataxia. • Diagnosis: Elevated plasma tyrosine, urine metabolites (4-hydroxyphenylpyruvic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylacetic acid).

Answer 38

Type 3:

Question 39

Types of Hereditary Tyrosinemia: Symptoms: Intellectual disability, seizures, intermittent ataxia. Diagnosis: Elevated plasma tyrosine, urine metabolites (4-hydroxyphenylpyruvic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylacetic acid).

Answer 39

Type 3

Question 40

Alkaptonuria Treatment to hinder homogentisic acid accumulation.

Answer 40

Vitamin C