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Questions and Answers
What is the primary purpose of newborn screening tests?
What is the primary purpose of newborn screening tests?
In which condition is the Guthrie Test particularly useful?
In which condition is the Guthrie Test particularly useful?
What dietary management is essential for individuals with Phenylketonuria (PKU)?
What dietary management is essential for individuals with Phenylketonuria (PKU)?
Tyrosine metabolism disorders typically result from deficiencies in which component?
Tyrosine metabolism disorders typically result from deficiencies in which component?
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What is a common feature of overflow metabolic disorders?
What is a common feature of overflow metabolic disorders?
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Which of the following conditions can result in an adrenal crisis in newborns?
Which of the following conditions can result in an adrenal crisis in newborns?
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Which screening test is used for detecting Glucose-6 phosphate dehydrogenase (G6PD) deficiency in newborns?
Which screening test is used for detecting Glucose-6 phosphate dehydrogenase (G6PD) deficiency in newborns?
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Abnormal urine color and odor may indicate the need for what?
Abnormal urine color and odor may indicate the need for what?
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What color change occurs when ferric chloride is added to urine containing phenylpyruvic acid?
What color change occurs when ferric chloride is added to urine containing phenylpyruvic acid?
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What is the primary method used for the urine testing of tyrosyluria?
What is the primary method used for the urine testing of tyrosyluria?
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Which dietary management strategy is recommended for patients with tyrosinemia?
Which dietary management strategy is recommended for patients with tyrosinemia?
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How does nitisinone contribute to the treatment of tyrosinemia?
How does nitisinone contribute to the treatment of tyrosinemia?
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In what condition can tyrosinemia in premature infants occur?
In what condition can tyrosinemia in premature infants occur?
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Which of the following is a degradation product of tyrosine that may be found in the urine?
Which of the following is a degradation product of tyrosine that may be found in the urine?
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Which metabolite's elevated level is confirmed during the diagnostic criteria for tyrosinemia?
Which metabolite's elevated level is confirmed during the diagnostic criteria for tyrosinemia?
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What is a common microscopic finding in urine sediment for tyrosyluria cases?
What is a common microscopic finding in urine sediment for tyrosyluria cases?
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What is the primary enzyme deficiency causing Tyrosinemia Type 1?
What is the primary enzyme deficiency causing Tyrosinemia Type 1?
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Which condition is characterized by corneal erosion and lesions on the palms, fingers, and soles?
Which condition is characterized by corneal erosion and lesions on the palms, fingers, and soles?
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What is the consequence of untreated Tyrosinemia Type 3?
What is the consequence of untreated Tyrosinemia Type 3?
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What indicates a potential malignancy when found elevated in urine?
What indicates a potential malignancy when found elevated in urine?
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What is the metabolic derivative of tyrosine that oxidizes to form melanin?
What is the metabolic derivative of tyrosine that oxidizes to form melanin?
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What laboratory finding is associated with alkaptonuria?
What laboratory finding is associated with alkaptonuria?
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Which of the following diseases results from a deficiency in an enzyme affecting the degradation of phenylalanine?
Which of the following diseases results from a deficiency in an enzyme affecting the degradation of phenylalanine?
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What test is typically used to screen for tyrosinemia by detecting tyrosine metabolites?
What test is typically used to screen for tyrosinemia by detecting tyrosine metabolites?
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Study Notes
Urine Screening for Metabolic Disorders
- Abnormal urinalysis results are often linked to metabolic, rather than renal, issues.
- Positive screening tests may necessitate more sophisticated lab procedures.
- Detections by lab personnel, abnormal colors, or odours of specimens might indicate a need for additional testing.
- Patient symptoms and family health histories are crucial diagnostic factors.
Overflow vs. Renal Disorders
- Overflow disorders stem from disruptions in normal metabolic pathways, causing elevated non-metabolized substances in the blood.
- Overflow substances exceed the reabsorption capacity of renal tubules and are not usually reabsorbed from the filtrate.
- Renal disorders arise from malfunctions in tubular reabsorption mechanisms.
Overflow – Continued
- Metabolic imbalances (protein, fat, and carbohydrate metabolism) can trigger overflow.
- Enzyme malfunctions, known as inborn errors of metabolism (IEM), can result from inherited gene defects.
Newborn Screening Tests
- Newborn screenings primarily detect and monitor inborn errors of metabolism (IEMs).
- The Philippine newborn screening tests have expanded from 6 to 28.
- Initial 6 include congenital hyperthyroidism, phenylketonuria, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia, and maple syrup disease.
Congenital Hyperthyroidism
- Excessive thyroid hormones can lead to stunted growth and intellectual disabilities.
Phenylketonuria (PKU)
- An inherited condition where children cannot process the amino acid phenylalanine.
- Undiagnosed PKU can cause severe mental retardation.
- First identified in Norway in 1934 by Ivan Følling.
- PKU patients often exhibit a peculiar "mousy" odor in their urine.
- Normal phenylalanine-to-tyrosine conversion is disrupted.
- Early intervention by dietary changes that eliminate phenylalanine prevents damage to the child's mental capabilities.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- An inherited condition that results in hemolytic anemia.
- This condition can be fatal if not treated properly.
Galactosemia
- Inability to metabolize galactose, a sugar found in breast milk.
- Untreated galactosemia can be life-threatening.
Maple Syrup Urine Disease (MSUD)
- Infants with MSUD cannot metabolize specific proteins.
- The condition typically presents with a maple-syrup odor in the urine.
- Left untreated, MSUD can lead to death.
Early Detection of Defects
- Early detection of metabolic defects is crucial to prevent the buildup of unmetabolized toxic substances.
- Blood levels are more rapidly elevated than urine levels in affected infants.
- Blood is collected by infant heel puncture for initial testing.
Amino Acid Disorders
- PKU is the most well-known of the aminoacidurias affecting 1 in every 10,000-20,000 births.
Tyrosinemia
- Accumulation of excess tyrosine in the blood (tyrosinemia) stems from inherited or metabolic defects.
- Two reactions are involved in tyrosine metabolism, and they might be affected in tyrosinemia.
- Urine might contain excessive tyrosine or its breakdown products.
Tyrosinemia Type 1
- Characterized by generalized renal tubular issues and progressive liver failure in infants soon after birth.
- Caused by low levels of the enzyme fumarylacetoacetate hydrolase.
Tyrosinemia Type 2
- Caused by tyrosine aminotransferase deficiency.
- Symptoms include corneal erosion and lesions on the palms, fingers, and soles.
- Crystallization of tyrosine occurs in the cells.
Tyrosinemia Type 3
- Deficit of p-hydroxyphenylpyruvic acid dioxygenase.
- May cause mental retardation if dietary phenylalanine/tyrosine restrictions aren't implemented.
Melanuria
- A second metabolic pathway exists to produce melanin.
- Melanin is the pigment in hair, skin, and eyes.
- Deficiency in melanin production leads to albinism.
- Elevated urinary melanin can indicate a serious proliferation of abnormal cells (malignant melanoma in particular.)
Alkaptonuria
- A genetic condition marked by darkening of urine after it becomes alkaline (due to the accumulation of homogentisic acid.)
- This is due to the failure to produce the required enzyme homogentisic acid oxidase, interfering with the phenylalanine-tyrosine pathway.
- Affected individuals may develop arthritis due to the deposition of the excess acid in cartilage.
Maple Syrup Urine Disease (MSUD)
- A lifelong metabolic disorder influencing how the body breaks down amino acids for energy, specifically affecting leucine, isoleucine, and valine.
- Classic, intermediate, intermittent, and thiamine-responsive MSUD types exist, each with distinct symptom presentation and severity.
MSUD Management
- Management involves dietary restrictions, especially limiting protein intake.
- Monitoring of amino acid levels regularly and timely intervention for metabolic crises are essential.
- Emergency support for metabolic crises (glucose and insulin) and nutritional support (NG tube, hemodialysis) might help manage the disorder.
PKU Treatment
- PKU treatment involves maintaining phenylalanine levels between 2 and 10 mg/dL (120-600 umol/L).
- A diet with reduced phenylalanine is crucial for PKU management.
MSUD Treatment
- MSUD management relies on dietary regulation and monitoring for excessive urinary keto acid buildup.
PKU Testing
- Early PKU detection might be missed in routine urinalysis as high blood phenylalanine levels often precede the noticeable urinary excretion of phenylpyruvic acid by several weeks.
- Blood collected 24 hrs after birth is used for testing now.
- Studies suggest detection can be as early as 4 hrs post-birth with lowered cutoff levels (2 mg/dL rather than 4 mg/dL for example.)
Urine Testing Procedures
- Ferric chloride tests are used to identify phenylpyruvic acid in urine, exhibiting a permanent blue-green color.
- Urine tests using nitroso-naphthol aid in identifying tyrosine metabolites, evident in an orange-red color.
- Brady's test (2,4-dinitrophenylhydrazine or DNPH) is a urine screening technique for MSUD, producing yellow turbidity or precipitates.
Newborn Screening Diagnostics
- Current newborn screening methods involve using tandem mass spectrometry (MS/MS) to detect a multitude of genetic disorders in a single sample, hence displacing other tests.
- Liquid chromatography combined with mass spectrometry (HPLC-MS/MS) and high-performance liquid chromatography (HPLC) are methods for determining phenylalanine levels from body fluids.
- The Guthrie bacterial inhibition assay (or "Guthrie test") is a semiquantitative measure for phenylalanine levels in newborns. Detections based on this technique might be inaccurate in cases of antibiotic use and blood exchange.
Diagnostic Criteria for Tyrosinemia
- Elevated tyrosine levels detected by MS/MS combined with confirmed higher succinylacetone levels.
- Urine testing for tyrosinemia usually involves using nitroso-naphthol, exhibiting an orange-red color upon testing for tyrosine metabolites.
Laboratory Procedures and Tests
- Detailed procedures of the ferric chloride test for detecting phenylpyruvic acid in urine and the nitroso-naphthol test for detecting tyrosine metabolites are provided.
- Diagnostic methods like the ferric chloride test, Clinitest, and homogentisic acid test are key for alkaptonuria assessment.
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