Screeng For Metabolic Disorders: Phenylalanine-Tyrosine disorders Flashcards
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
Overflow disorders
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.
inborn error of metabolism (IEM)
organ malfunctio
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.
tandem mass spectrophotometry (MS/MS)
Amino Acid Disorders
The amino acid disorders with urinary screening tests include (9)
PTMAM O ICC
phenylketonuria (PKU)
tyrosyluria
melanuria
alkaptonuria
maple syrup urine disease (MSUD)
organic acidemias
indicanuria
cystinuria
cystinosis
Major inherited disorders include.
Metabolic defects cause overproduction of melanin.
PKU, tyrosyluria, and alkaptonuria
Phenylalanine-Tyrosine Disorders
• Metabolic disturbances that produce substances involved in protein, fat, and carbohydrate metabolism
• Vast number of involved enzymes
OVERFLOW DISORDERS
• Main cause: disruption of enzyme function
• Failure to inherit the gene that produces the enzyme
• Organ malfunction from disease or toxic reactions
OVERFLOW DISORDERS
• Traditionally performed to detect and monitor newborns for any inborn error of metabolism
•_____ tests performed in the expanded newborn screening (before: 6)
NEWBORN SCREENING TESTS
29
METABOLIC DISORDERS
• AMINO ACID DISORDERS
• PORPHYRIN DISORDERS
• MUCOPOLYSACCHARIDE DISORDERS
• PURINE DISORDERS
• CARBODHYRATE DISORDERS
Phenylalanine-Tyrosine disorders
PMAT
• Phenylketonuria
• Melanuria
• Alkaptonuria
• Tyrosyluria
• Branched-chain amino acid disorders
• MSUD
• Organic acidemias
• Tryptophan disorders
• Indicanuria
• 5-hydroxyindoleacetic acid
• Cystine disorders
• Cystinuria
• Cystinosis
• Homocystinuria
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_______
mental retardation
myelination
Mousy
phenylalanine
PHENYLKETONURIA
• Increased phenylalanine levels due to defective or absent_____
• Phenylalanine is converted instead into _______which may also be detected
phenylalanine hydroxylase
phenylpyruvic acid
URINE TEST FOR PHENYLKETONURIA
•_________
Ferric chloride tube test
Ferric chloride acid test for PKU
• Detects _______
• 5 drops of______ to 1 mL of____
• A permanent_____ color is positive
phenylpyruvic acid
10% ferric chloride; urine
blue-green
• Accumulation of excess tyrosine in the plasma (tyrosinemia) produces urinary overflow
TYROSYLURIA
TYROSYLURIA
p-hydroxyphenylpyruvic acid dioxygenase
• Tyrosinemia type 3:
TYROSYLURIA
tyrosine aminotransferase
• Tyrosinemia type 2:
TYROSYLURIA
fumarylacetate hydrolase
• Tyrosinemia Type 1 :
• Results into mental retardation if dietary restrictions of phenylalanine and tyrosine are not implemented
Tyrosyluria
URINE TEST FOR TYROSYLURIA
Nitroso-naphthol test
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
urine;
2.63 N nitric acid;
21.5% sodium nitrite;
nitroso-2-naphthol
Orange-red
MELANURIA
•________: product of a second metabolic pathway for tyrosine
• Deficient production of melanin results in______
• Increased levels of melanin:____
Melanin
albinism
melanuria
MELANURIA
• Proliferation of______ which produces melanoma
• Cancer cells produce_____ which oxidizes to melanogen and then to melanin
melanocytes
5,6-dihydroxyindole
Urine darkens upon exposure to air
MELANURIA
ALKAPTONURIA
• Failure to inherit the gene that codes for the enzyme_______
homogentisic acid oxidase
• Urine darkens/turns to black upon standing
LAKAPTONURIA
• Accumulation of homogentisic acid in blood, tissues, and urine
ALKAPTONURIA
• 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
ALKALTONURIA
URINE TESTS FOR ALKAPTONURIA
• Ferric chloride test
• Clinitest
• Homogentisic acid test
URINE TESTS FOR ALKAPTONURIA
• Ferric chloride test:_____
• Clinitest:_____
• Homogentisic acid test:____
deep blue color
yellow precipitate
Observe for black color
PKU
• Treatment:
• Dietary control to limit phenylalanine (found in milk).
• Avoid products containing aspartame (found in diet foods, sodas, etc.).
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.
24–48 hours
4 hours
Types of Hereditary Tyrosinemia:
• Leads to renal tubular disorder and progressive liver failure.
• Diagnosis: Tyrosine and succinylacetone in urine/blood, genetic testing.
Type 1
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.
Type 2
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).
Type 3:
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).
Type 3
Alkaptonuria
Treatment to hinder homogentisic acid accumulation.
Vitamin C
