7.1 METABOLIC DISORDERS - INTRO, AMINO ACID DISORDERS Flashcards
What are most abnormal results in routine urinalysis related to?
Metabolic diseases
What can urine as an end product of body metabolism contain that is not tested in routine urinalysis?
Additional abnormal substances.
How can additional abnormal substances in urine be detected?
Additional screening tests
What can positive screening tests be followed by?
Sophisticated procedures in other lab sections.
What observations can indicate the need for additional urine tests?
Abnormal specimen color and odor or clinical symptoms and family histories.
What are the two categories of disorders that cause abnormal metabolic substances in urine?
Overflow disorders and renal disorders
Disruption of normal metabolic pathways leading to increased plasma concentrations of nonmetabolized substances.
overflow disorders
Malfunctions in the tubular reabsorption mechanism.
renal disorders
What types of metabolic disturbances most frequently produce urinary overflow?
Disturbances in the metabolism of protein, fat, and carbohydrates
What can disrupt enzyme function in metabolic pathways?
Inborn errors of metabolism (IEMs) or organ malfunction.
Failure to inherit the gene to produce a particular enzyme
inborn error of metabolism (IEM)
What was the traditional purpose of many urine tests discussed in this chapter?
Detecting and monitoring newborns for IEMs.
How many core conditions and secondary target conditions do many states mandate newborn screening for?
31 core conditions and 25 secondary target conditions.
Why is early detection of defects causing IEMs important?
To prevent the buildup of unmetabolized toxic food ingredients
In IEM detection, where are elevated levels of substances detected more rapidly?
In blood
What method is primarily used for testing infant blood for IEMs?
Tandem mass spectrophotometry (MS/MS).
What does MS/MS screening detect?
Specific substances associated with particular IEMs.
What is being developed rapidly for detecting IEMs?
Specific gene testing methods.
What are the subgroups of disorders under amino acid disorders?
Phenylalanine-tyrosine disorders,
branched-chain amino acid disorders, tryptophan disorders, and
cystine disorders.
What are the disorders under phenylalanine-tyrosine disorders?
Phenylketonuria (PKU),
tyrosyluria,
melanuria, and
alkaptonuria.
What metabolic defect results in overproduction of melanin?
Phenylalanine-tyrosine disorders
What are the disorders under branched-chain amino acid disorders?
Maple syrup urine disease (MSUD) and
organic acidemias (isovaleric, propionic, and methylmalonic acidemia).
What are the disorders under tryptophan disorders?
Indicanuria and
5-hydroxyindoleacetic acid (5-HIAA) overproduction.
What are the disorders under cystine disorders?
Cystinuria and cystinosis.
What disorder is characterized by a failure to inherit the enzyme phenylalanine hydroxylase, resulting in intellectual disability if untreated?
Phenylketonuria (PKU).
Which disease produces a “mousy odor” in urine and sweat due to phenylpyruvic acid accumulation?
Phenylketonuria (PKU)
What autosomal recessive disorder leads to reduced melanin production, causing lighter skin and hair in affected individuals?
Phenylketonuria (PKU).
What symptom is commonly observed in infants with PKU?
Mousy odor in urine and sweat.
How is PKU screened in newborns?
By testing blood phenylalanine levels between 24–48 hours after birth
Which disease results in tyrosine accumulation due to enzyme deficiencies or immature liver function in newborns?
Tyrosyluria
What type of tyrosinemia involves a deficiency in the enzyme fumarylacetoacetate hydrolase and causes renal and liver failure in infants?
Tyrosinemia Type 1
What disease is caused by a deficiency in tyrosine aminotransferase, leading to corneal erosions and skin lesions?
Tyrosinemia Type 2.
Which type of tyrosinemia is characterized by intellectual disability and ataxia due to a lack of p-hydroxyphenylpyruvic acid dioxygenase?
Tyrosinemia Type 3.
What causes type 1 tyrosinemia?
Deficiency of fumarylacetoacetate hydrolase (FAH).
What are the symptoms of type 2 tyrosinemia?
Corneal erosions and skin lesions on palms and soles.
Which metabolite is elevated in type 3 tyrosinemia?
4-hydroxyphenylpyruvic acid.
What indicates increased melanin production in urine?
Dark urine after exposure to air.
Which condition is associated with malignant melanocytes?
Melanuria
Which disorder results from a deficiency in homogentisic acid oxidase, leading to black-stained urine and ochronosis?
Alkaptonuria
What autosomal recessive disorder involves brown pigment deposits in tissues and can lead to arthritis and cardiac complications?
Alkaptonuria
What enzyme deficiency causes alkaptonuria?
Homogentisic acid oxidase.
What classic symptom is seen in alkaptonuria?
Dark urine upon standing at room temperature.
Which amino acids accumulate in MSUD?
Leucine, isoleucine, and valine.
What is the characteristic urine odor in MSUD?
Maple syrup-like smell.
Which disease produces a sweet, “maple syrup” odor in urine due to branched-chain keto acid accumulation?
Maple Syrup Urine Disease (MSUD).
Which branched-chain amino acid disorder causes a “sweaty feet” odor in urine due to isovalerylglycine accumulation?
Isovaleric Acidemia.
What common metabolic defect is shared by propionic and methylmalonic acidemia?
Errors in converting amino acids to succinyl CoA.
Which organic acidemia disorders result from defects in the conversion of isoleucine, valine, threonine, and methionine to succinyl CoA?
Propionic acidemia and methylmalonic acidemia
What disorder causes blue-stained diapers (blue diaper syndrome) due to excessive indican in urine?
Indicanuria (associated with Hartnup disease).
What disorder is associated with carcinoid tumors and increased serotonin metabolism, resulting in elevated urinary 5-HIAA?
5-Hydroxyindoleacetic Acid (5-HIAA) elevation.
Intestinal disorders leading to increased tryptophan metabolism to indole
indicanuria
What tumor is associated with elevated 5-HIAA levels?
Argentaffin cell (carcinoid) tumors.
What dietary items interfere with 5-HIAA testing?
Bananas, avocados, tomatoes, and walnuts.
What is the main defect in cystinuria?
Failure to reabsorb cystine in renal tubules.
What is the primary manifestation of cystinuria?
Formation of cystine renal calculi
What disorder involves a renal tubular defect leading to poor reabsorption of cystine and potential formation of cystine kidney stones?
Cystinuria
Which inherited disorder results in cystine accumulation in lysosomes, causing organ damage?
Cystinosis
What is cystinosis characterized by?
Intracellular accumulation of cystine in lysosomes.
What systemic effects are associated with cystinosis?
Renal failure and growth retardation
What dietary intervention is critical for managing PKU?
Eliminating phenylalanine from the diet.
Which screening test detects phenylpyruvic acid in PKU patients?
Ferric chloride test.
What test is used to detect tyrosyluria by reacting with nitroso-naphthol?
Qualitative urine screening test.
What test produces a deep blue color when detecting homogentisic acid in urine?
Ferric chloride test
What is the specific genetic mutation responsible for most cases of PKU?
Mutations in the PAH (phenylalanine hydroxylase) gene
What is the key cofactor required by phenylalanine hydroxylase that can also be deficient in some cases of PKU?
Tetrahydrobiopterin (BH4).
What are the common clinical features of untreated PKU in infants?
Intellectual disability, microcephaly, seizures, and behavioral problems.
What newborn screening method is commonly used to detect PKU?
Guthrie bacterial inhibition assay
What amino acid becomes essential in patients with PKU?
Tyrosine
What metabolic byproduct is elevated in the urine of patients with tyrosyluria?
Tyrosine and its derivatives, such as p-hydroxyphenylpyruvic acid.
What is a distinguishing feature of Type 1 tyrosinemia compared to other types?
Presence of succinylacetone in the urine.
What medication is used to treat Type 1 tyrosinemia by inhibiting the production of toxic metabolites?
Nitisinone (NTBC)
What enzyme deficiency causes Type 2 tyrosinemia?
Tyrosine aminotransferase
What characteristic clinical symptom is associated with Type 2 tyrosinemia?
Painful keratotic plaques on the palms and soles
What color does homogentisic acid turn when exposed to air?
Black
What long-term complication of alkaptonuria affects the heart?
Calcification of heart valves
Which connective tissue condition is associated with ochronosis in alkaptonuria?
Arthritis, especially in large weight-bearing joints.
What laboratory test can confirm the presence of homogentisic acid in urine?
Benedict’s test or chromatography techniques
Which enzyme complex is deficient in MSUD?
Branched-chain alpha-keto acid dehydrogenase (BCKD) complex
What are the three amino acids that accumulate in MSUD?
Leucine, isoleucine, and valine
What is the common clinical presentation of MSUD in neonates?
Poor feeding, vomiting, lethargy, and sweet-smelling urine.
What dietary treatment is essential for MSUD management?
A low-protein diet with restricted intake of branched-chain amino acids
Which amino acid is the primary contributor to neurotoxicity in MSUD?
Leucine
What enzyme deficiency causes isovaleric acidemia?
Isovaleryl-CoA dehydrogenase.
What triggers acute metabolic crises in isovaleric acidemia?
High protein intake or infection.
What treatment can help neutralize accumulated organic acids in isovaleric acidemia?
Glycine or carnitine supplementation
What dietary deficiency exacerbates symptoms of Hartnup disease?
Niacin (vitamin B3).
What is the source of the blue discoloration in “blue diaper syndrome”?
Indican oxidized to indigo blue.
Which amino acid’s absorption is defective in Hartnup disease?
Tryptophan
What neurological symptoms are associated with Hartnup disease?
Ataxia, photodermatitis, and mental changes
What amino acids are poorly reabsorbed in cystinuria?
Cystine, lysine, arginine, and ornithine.
What is the most common clinical manifestation of cystinuria?
Recurrent cystine kidney stones
What test is used to diagnose cystinuria by detecting cystine in urine?
Cyanide-nitroprusside test.
What medication is used to increase cystine solubility and reduce stone formation in cystinuria?
Penicillamine
What organ is most affected in nephropathic cystinosis?
Kidneys, leading to Fanconi syndrome
What intracellular structure accumulates cystine in cystinosis?
Lysosomes
What is the primary treatment for cystinosis to prevent cystine accumulation?
Cysteamine therapy
What complication of cystinosis often appears in adulthood?
Retinal blindness.
