Untitled Quiz

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.