Clinical Chemistry Ii Test 3 - Inherited Metabolic Disorders

Front 1

What is the multistep process of identification of a inherited metabolic disorder of a newborn?

Back 1

Blood specimens from infants are analyzed by the laboratory
If a result is abnormal, laboratory staff notifies case management staff
Case management provides follow-up to assist linking families with appropriate providers to
Confirm the test results and
Ensure the infant has the disorder prior to treatment
Ensure the infant receives appropriate treatment

Front 2

When are the two newborn screens done?

Back 2

The first screen at 24-48 hours or before leaving hospital, whichever is first
The second screen at 1-2 weeks of age
Via 2 drops of blood from heel stick on filter paper. Blood extracted.

Front 3

What is congenital hypothyroidism?

Back 3

Inability of infant to produce adequate amount of thyroid hormone which causes cretinism
Most common and preventable cause of mental retardation in infants
1 in 2,000 TX newborns
Treatment is life-long thyroid replacement therapy

Front 4

What is adrenal hyperplasia and/or adrenogenital syndrome?

Back 4

Inborn error of steroid biosynthesis that causes a lack of cortisol production and may also cause lack of Aldosterone production.
Deficiency in 21-hydroxylase is the cause of 90 –95% of cases.

Front 5

What are the two consequences of Adrenal Hyperplasia and/or adrenogenital syndrome as?

Back 5

Salt wasting type--severe dehydration which leads to adrenal crisis
Virilizing type—increased fetal adrenal androgens

Front 6

What is renal aminoaciduria?

Back 6

Increased urine amino acid concentration due to deficiency in active transport molecule that is responsible for reabsorbing the class of amino acids from the proximal convoluted tubule.
Serum concentration is normal to decreased (excessive loss)

Front 7

What are two examples of renal aminoaciduria?

Back 7

Cystinuria and Hartnup syndrome

Front 8

What is cystinuria?

Back 8

Inherited as an autosomal recessive disorder
Lack of transport molecule to reabsorb cysteine, ornithine, lysine, arginine (COLA).
Excess of poorly-soluble cysteine in urine which goes to renal calculi (recur following removal)

Front 9

What are lab findings for cystinuria?

Back 9

Laboratory findings—colorless, hexagonal cysteine crystals in acid urine

Front 10

How do you treat cyctinuria?

Back 10

Treatment is restricted diet, hydration, maintaining pH above 7.5, chelation and surgery.

Front 11

What is Hartnup syndrome?

Back 11

Unable to reabsorb neutral amino acids from PCT due to deficient transport molecule.

Front 12

What is overflow aciduria

Back 12

Increased blood concentration due to deficiency in the metabolic pathway of a amino acid;
Increased concentration in urine is due to "overflow".

Front 13

What are some examples of overflow aciduria?

Back 13

PKU, Tyrosinemia, Alkaptonuria, Albinism, Maple syrup urine disease (MSUD) and homocystinuria.

Front 14

What is Phenylketonuria (PKU)?

Back 14

Deficient phenylalinine-hydroxylase which is required to converted phe into tyr.
High concentration of phe in plasma and urine leads to abnormal metabolites appear in urine = phenylketones (phenyl-lactic, phenyl-pyruvic, phenyl-acetic acid)

Front 15

What physical symptoms do infants with PKU display?

Back 15

Infants appear normal at birth but eventually display symptoms such as musty odor.
Undiagnosed and untreated will result in developmental delay in first year of life, followed by severe mental retardation and hypopigmentation.

Front 16

How is PKU treated?

Back 16

Eliminate phe from diet to prevent problem.

Front 17

What test is used to screen newborns for PKU?

Back 17

Guthrie test

Front 18

What is the Guthrie Test?

Back 18

Spores of B.Subtilis are pre-seeded on agar medium deficient in phe. A disk containing -2-thienylanine is placed on the culture media.
Normally, Beta-2-thienylalinine inhibits this strain but increased concentrations of phe allow the organism to overcome the inhibition and grow.
Incubate aliquots of patient’s serum (blood-soaked filter paper) on the agar overnight, and look for growth.
Growth of bacteria = excessive phe in patient's serum
Initial results require confirmation by quantitative serum phe analysis -- >6 mg/dL requires dietary restrictions.

Front 19

What precautions must pregnant woman whom have PKU take?

Back 19

Women who have ceased dietary restriction of phe will give birth to infants already compromised and mentally retarded.

Women must return to restricted diets prior to conception and throughout the pregnancy.

Front 20

What is Tyrosinemia?

Back 20

Elevated tyrosine in blood and urine
Enzyme deficiency in metabolic pathway
Tyrosine aminotransferase

Front 21

What is Alkaptonuria?

Back 21

Lack of homogentisic acid oxidase which causes a build up of homgentisic acid which develops dark blue or black deposits in cartilage
Urine becomes dark upon standing or addition of a base (alkaline PH)

Front 22

What is albinism?

Back 22

Absence of tyrosinase, enzyme that converts tyrosine to melanin.
Lack of pigment—poor eye sight, lack of color of hair, skin and eyes.

Front 23

What is Maple Syrup Urine Disease?

Back 23

Branched chain aminoaciduria
Deficient enzyme, Keto acid decarboxylase, for metabolism of leu, isoleucine (ise) and val
Metabolites accumulate ketone derivatives which cause odor of maple syrup in sweat, urine etc.
Severe mental retardation can occur within the first week of life.
Dietary restriction is ineffective.

Front 24

What is Homocystinuria?

Back 24

Deficiency of cystathionine synthase, enzyme which converts homosysteine to cystathionine.
Enzyme deficiency specially effects methionine regeneration.
Infants appear normal at birth but symptoms appear with age—mental retardation, osteoperosis.
Treatment is folic acid and Vitamin B12

Front 25

What is Galactosemia?

Back 25

Deficiency of enzymes required to convert galacatose to glucose which causes a side-reactions cause accumulation of galactitol which is neurotoxic.

Front 26

What tests are used to monitor galactosemia?

Back 26

Routine urinalysis of patients <2 yrs old includes reducing substance test (Clinitest—copper reduction test) even if glucose in urine is negative.
Dipstick uses glucose substrate specific glucose oxidase and does not detect reducing sugars
Copper reduction test detects other reducing sugars such as galactose.

Front 27

What can be done to prevent symptoms of galactosemia?

Back 27

Early detection of galactosemia can lead to removal of lactose and galactose from diet and prevent retardation, cirrhosis and cataract.

Front 28

What are glycogen storage diseases?

Back 28

Glycogen storage diseases such as type I (von Gierke’s disease) are rare disorders due to enzyme defects and accumulation of glycogen in liver and skeletal muscle.

Front 29

What is type I GSD?

Back 29

Type I: glucose-6-phosphatase deficiency
glycogenolysis, hypoglycemia during fasting states, growth retardation, ketosis, lactic acidosis, and hepatomegaly

Front 30

What is type II, V, VII GSD?

Back 30

Types II, V, and VII: other enzyme defects
milder symptoms; accumulation of glycogen primarily in skeletal muscle

Front 31

What is type III and VI GSD?

Back 31

Types III and VI: liver forms of glycogen storage disease; rare

Front 32

What is type IV GSD?

Back 32

Type IV: severe liver form of glycogen storage disease
cardiac and skeletal muscle disease

Front 33

What are some lipid abnormalities?

Back 33

Deficient enzymes responsible for metabolizing different fatty acids.

Disorders of glycolipids—abnormal lipid storage which inhibits body’s ability to utilize stored fat.

Front 34

What is cystic fibrosis?

Back 34

Deficient transmembrane protein results in extremely viscous secretions, lung disease, pancreatic insufficiency

Front 35

What is the procedure for a CF diagnostic screening test?

Back 35

Diagnostic screening test for increased Cl in sweat
1st inject pilocarpine (to stimulate sweat glands) into skin
2nd collect 50 - 100 L of sweat and measure Cl- conc
 3rd calculate mmol/L sweat Cl-
cystic fibrosis > 60 mmol/L
normal < 35
retest 35-60