7.1 METABOLIC DISORDERS - INTRO, AMINO ACID DISORDERS

Question 1

What are most abnormal results in routine urinalysis related to?

Answer 1

Metabolic diseases

Question 2

What can urine as an end product of body metabolism contain that is not tested in routine urinalysis?

Answer 2

Additional abnormal substances.

Question 3

How can additional abnormal substances in urine be detected?

Answer 3

Additional screening tests

Question 4

What can positive screening tests be followed by?

Answer 4

Sophisticated procedures in other lab sections.

Question 5

What observations can indicate the need for additional urine tests?

Answer 5

Abnormal specimen color and odor or clinical symptoms and family histories.

Question 6

What are the two categories of disorders that cause abnormal metabolic substances in urine?

Answer 6

Overflow disorders and renal disorders

Question 7

Disruption of normal metabolic pathways leading to increased plasma concentrations of nonmetabolized substances.

Answer 7

overflow disorders

Question 8

Malfunctions in the tubular reabsorption mechanism.

Answer 8

renal disorders

Question 9

What types of metabolic disturbances most frequently produce urinary overflow?

Answer 9

Disturbances in the metabolism of protein, fat, and carbohydrates

Question 10

What can disrupt enzyme function in metabolic pathways?

Answer 10

Inborn errors of metabolism (IEMs) or organ malfunction.

Question 11

Failure to inherit the gene to produce a particular enzyme

Answer 11

inborn error of metabolism (IEM)

Question 12

What was the traditional purpose of many urine tests discussed in this chapter?

Answer 12

Detecting and monitoring newborns for IEMs.

Question 13

How many core conditions and secondary target conditions do many states mandate newborn screening for?

Answer 13

31 core conditions and 25 secondary target conditions.

Question 14

Why is early detection of defects causing IEMs important?

Answer 14

To prevent the buildup of unmetabolized toxic food ingredients

Question 15

In IEM detection, where are elevated levels of substances detected more rapidly?

Answer 15

In blood

Question 16

What method is primarily used for testing infant blood for IEMs?

Answer 16

Tandem mass spectrophotometry (MS/MS).

Question 17

What does MS/MS screening detect?

Answer 17

Specific substances associated with particular IEMs.

Question 18

What is being developed rapidly for detecting IEMs?

Answer 18

Specific gene testing methods.

Question 19

What are the subgroups of disorders under amino acid disorders?

Answer 19

Phenylalanine-tyrosine disorders,
branched-chain amino acid disorders, tryptophan disorders, and
cystine disorders.

Question 20

What are the disorders under phenylalanine-tyrosine disorders?

Answer 20

Phenylketonuria (PKU),
tyrosyluria,
melanuria, and
alkaptonuria.

Question 21

What metabolic defect results in overproduction of melanin?

Answer 21

Phenylalanine-tyrosine disorders

Question 22

What are the disorders under branched-chain amino acid disorders?

Answer 22

Maple syrup urine disease (MSUD) and

organic acidemias (isovaleric, propionic, and methylmalonic acidemia).

Question 23

What are the disorders under tryptophan disorders?

Answer 23

Indicanuria and
5-hydroxyindoleacetic acid (5-HIAA) overproduction.

Question 24

What are the disorders under cystine disorders?

Answer 24

Cystinuria and cystinosis.

Question 25

What disorder is characterized by a failure to inherit the enzyme phenylalanine hydroxylase, resulting in intellectual disability if untreated?

Answer 25

Phenylketonuria (PKU).

Question 26

Which disease produces a "mousy odor" in urine and sweat due to phenylpyruvic acid accumulation?

Answer 26

Phenylketonuria (PKU)

Question 27

What autosomal recessive disorder leads to reduced melanin production, causing lighter skin and hair in affected individuals?

Answer 27

Phenylketonuria (PKU).

Question 28

What symptom is commonly observed in infants with PKU?

Answer 28

Mousy odor in urine and sweat.

Question 29

How is PKU screened in newborns?

Answer 29

By testing blood phenylalanine levels between 24–48 hours after birth

Question 30

Which disease results in tyrosine accumulation due to enzyme deficiencies or immature liver function in newborns?

Answer 30

Tyrosyluria

Question 31

What type of tyrosinemia involves a deficiency in the enzyme fumarylacetoacetate hydrolase and causes renal and liver failure in infants?

Answer 31

Tyrosinemia Type 1

Question 32

What disease is caused by a deficiency in tyrosine aminotransferase, leading to corneal erosions and skin lesions?

Answer 32

Tyrosinemia Type 2.

Question 33

Which type of tyrosinemia is characterized by intellectual disability and ataxia due to a lack of p-hydroxyphenylpyruvic acid dioxygenase?

Answer 33

Tyrosinemia Type 3.

Question 34

What causes type 1 tyrosinemia?

Answer 34

Deficiency of fumarylacetoacetate hydrolase (FAH).

Question 35

What are the symptoms of type 2 tyrosinemia?

Answer 35

Corneal erosions and skin lesions on palms and soles.

Question 36

Which metabolite is elevated in type 3 tyrosinemia?

Answer 36

4-hydroxyphenylpyruvic acid.

Question 37

What indicates increased melanin production in urine?

Answer 37

Dark urine after exposure to air.

Question 38

Which condition is associated with malignant melanocytes?

Answer 38

Melanuria

Question 39

Which disorder results from a deficiency in homogentisic acid oxidase, leading to black-stained urine and ochronosis?

Answer 39

Alkaptonuria

Question 40

What autosomal recessive disorder involves brown pigment deposits in tissues and can lead to arthritis and cardiac complications?

Answer 40

Alkaptonuria

Question 41

What enzyme deficiency causes alkaptonuria?

Answer 41

Homogentisic acid oxidase.

Question 42

What classic symptom is seen in alkaptonuria?

Answer 42

Dark urine upon standing at room temperature.

Question 43

Which amino acids accumulate in MSUD?

Answer 43

Leucine, isoleucine, and valine.

Question 44

What is the characteristic urine odor in MSUD?

Answer 44

Maple syrup-like smell.

Question 45

Which disease produces a sweet, "maple syrup" odor in urine due to branched-chain keto acid accumulation?

Answer 45

Maple Syrup Urine Disease (MSUD).

Question 46

Which branched-chain amino acid disorder causes a "sweaty feet" odor in urine due to isovalerylglycine accumulation?

Answer 46

Isovaleric Acidemia.

Question 47

What common metabolic defect is shared by propionic and methylmalonic acidemia?

Answer 47

Errors in converting amino acids to succinyl CoA.

Question 48

Which organic acidemia disorders result from defects in the conversion of isoleucine, valine, threonine, and methionine to succinyl CoA?

Answer 48

Propionic acidemia and methylmalonic acidemia

Question 49

What disorder causes blue-stained diapers (blue diaper syndrome) due to excessive indican in urine?

Answer 49

Indicanuria (associated with Hartnup disease).

Question 50

What disorder is associated with carcinoid tumors and increased serotonin metabolism, resulting in elevated urinary 5-HIAA?

Answer 50

5-Hydroxyindoleacetic Acid (5-HIAA) elevation.

Question 51

Intestinal disorders leading to increased tryptophan metabolism to indole

Answer 51

indicanuria

Question 52

What tumor is associated with elevated 5-HIAA levels?

Answer 52

Argentaffin cell (carcinoid) tumors.

Question 53

What dietary items interfere with 5-HIAA testing?

Answer 53

Bananas, avocados, tomatoes, and walnuts.

Question 54

What is the main defect in cystinuria?

Answer 54

Failure to reabsorb cystine in renal tubules.

Question 55

What is the primary manifestation of cystinuria?

Answer 55

Formation of cystine renal calculi

Question 56

What disorder involves a renal tubular defect leading to poor reabsorption of cystine and potential formation of cystine kidney stones?

Answer 56

Cystinuria

Question 57

Which inherited disorder results in cystine accumulation in lysosomes, causing organ damage?

Answer 57

Cystinosis

Question 58

What is cystinosis characterized by?

Answer 58

Intracellular accumulation of cystine in lysosomes.

Question 59

What systemic effects are associated with cystinosis?

Answer 59

Renal failure and growth retardation

Question 60

What dietary intervention is critical for managing PKU?

Answer 60

Eliminating phenylalanine from the diet.

Question 61

Which screening test detects phenylpyruvic acid in PKU patients?

Answer 61

Ferric chloride test.

Question 62

What test is used to detect tyrosyluria by reacting with nitroso-naphthol?

Answer 62

Qualitative urine screening test.

Question 63

What test produces a deep blue color when detecting homogentisic acid in urine?

Answer 63

Ferric chloride test

Question 64

What is the specific genetic mutation responsible for most cases of PKU?

Answer 64

Mutations in the PAH (phenylalanine hydroxylase) gene

Question 65

What is the key cofactor required by phenylalanine hydroxylase that can also be deficient in some cases of PKU?

Answer 65

Tetrahydrobiopterin (BH4).

Question 66

What are the common clinical features of untreated PKU in infants?

Answer 66

Intellectual disability, microcephaly, seizures, and behavioral problems.

Question 67

What newborn screening method is commonly used to detect PKU?

Answer 67

Guthrie bacterial inhibition assay

Question 68

What amino acid becomes essential in patients with PKU?

Answer 68

Tyrosine

Question 69

What metabolic byproduct is elevated in the urine of patients with tyrosyluria?

Answer 69

Tyrosine and its derivatives, such as p-hydroxyphenylpyruvic acid.

Question 70

What is a distinguishing feature of Type 1 tyrosinemia compared to other types?

Answer 70

Presence of succinylacetone in the urine.

Question 71

What medication is used to treat Type 1 tyrosinemia by inhibiting the production of toxic metabolites?

Answer 71

Nitisinone (NTBC)

Question 72

What enzyme deficiency causes Type 2 tyrosinemia?

Answer 72

Tyrosine aminotransferase

Question 73

What characteristic clinical symptom is associated with Type 2 tyrosinemia?

Answer 73

Painful keratotic plaques on the palms and soles

Question 74

What color does homogentisic acid turn when exposed to air?

Answer 74

Black

Question 75

What long-term complication of alkaptonuria affects the heart?

Answer 75

Calcification of heart valves

Question 76

Which connective tissue condition is associated with ochronosis in alkaptonuria?

Answer 76

Arthritis, especially in large weight-bearing joints.

Question 77

What laboratory test can confirm the presence of homogentisic acid in urine?

Answer 77

Benedict’s test or chromatography techniques

Question 78

Which enzyme complex is deficient in MSUD?

Answer 78

Branched-chain alpha-keto acid dehydrogenase (BCKD) complex

Question 79

What are the three amino acids that accumulate in MSUD?

Answer 79

Leucine, isoleucine, and valine

Question 80

What is the common clinical presentation of MSUD in neonates?

Answer 80

Poor feeding, vomiting, lethargy, and sweet-smelling urine.

Question 81

What dietary treatment is essential for MSUD management?

Answer 81

A low-protein diet with restricted intake of branched-chain amino acids

Question 82

Which amino acid is the primary contributor to neurotoxicity in MSUD?

Answer 82

Leucine

Question 83

What enzyme deficiency causes isovaleric acidemia?

Answer 83

Isovaleryl-CoA dehydrogenase.

Question 84

What triggers acute metabolic crises in isovaleric acidemia?

Answer 84

High protein intake or infection.

Question 85

What treatment can help neutralize accumulated organic acids in isovaleric acidemia?

Answer 85

Glycine or carnitine supplementation

Question 86

What dietary deficiency exacerbates symptoms of Hartnup disease?

Answer 86

Niacin (vitamin B3).

Question 87

What is the source of the blue discoloration in "blue diaper syndrome"?

Answer 87

Indican oxidized to indigo blue.

Question 88

Which amino acid's absorption is defective in Hartnup disease?

Answer 88

Tryptophan

Question 89

What neurological symptoms are associated with Hartnup disease?

Answer 89

Ataxia, photodermatitis, and mental changes

Question 90

What amino acids are poorly reabsorbed in cystinuria?

Answer 90

Cystine, lysine, arginine, and ornithine.

Question 91

What is the most common clinical manifestation of cystinuria?

Answer 91

Recurrent cystine kidney stones

Question 92

What test is used to diagnose cystinuria by detecting cystine in urine?

Answer 92

Cyanide-nitroprusside test.

Question 93

What medication is used to increase cystine solubility and reduce stone formation in cystinuria?

Answer 93

Penicillamine

Question 94

What organ is most affected in nephropathic cystinosis?

Answer 94

Kidneys, leading to Fanconi syndrome

Question 95

What intracellular structure accumulates cystine in cystinosis?

Answer 95

Lysosomes

Question 96

What is the primary treatment for cystinosis to prevent cystine accumulation?

Answer 96

Cysteamine therapy

Question 97

What complication of cystinosis often appears in adulthood?

Answer 97

Retinal blindness.