Inherited Metabolic Disorders

Front 1

List inherited disordres tested by state new born screening programs?

Back 1

29 disorders

1.) organic disorders

2.) fatty acid oxidation disorders

3.)amino acid disorders

4.) Sickling hemoglobinapahties, sickle cell

5.) Galactosemia 1 phosphate uridyltransferase defiency

6.)Endocrine disorders

7.) Cystic fibrosis

8.)Biotinidase defiency

Front 2

Texas babies are mandated to have what?

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2 newborn screens.:

1.) 1st screen at 1-2 days or before leaving hospital, whichever first.

2.) Second screen 1-2 weeks

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Criteria for screened disorders is?

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-significant frequency

-test inexpensive/reliable

-effective treatment/intervention exists

-if untreated, baby may die or mental retardation

-affected baby may appear norma at birth

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Fatty acid oxidation disorders include:

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- MCAD medium chain acyl COA dehydrogenase deficiency

-VLCAD - very long chain

-LCHAD long chain

-TFP: trifunctional protein defiency

-CUD: carnitine uptake them

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Amino acid metabolism disorder include:

Back 5

PKU- phenylketonuria
MSUD- maple syrup urine disease
HCY-homocystnuria
TYR I- tyrosinemia type 1

alkaponturnia

albinism

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Hemoglobinopathies disorders include:

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SCA- sickle cell anemia

-HB S beta thallesemia

-Hb S/C disease

Front 7

Other disorders include?

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-Hypoth-(CH) congenital hypothyroidsim

-CAH- congenital adrenal hyperplasia

-GALT- galactosemia

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Congenital Hypothyroidism (CH)

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-most common and preventable cause of mental retardation
-inability to produce thyroid hormone = cretinism
-treatment = life long thyroid replacement

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Adrenal Hyperplasia /adrenogenital syndrome

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-more like addison's disorder

-inborn error of steroid biosynthesis = lack of cortisol production & aldosterone.

-defiency 21 hydroxylase

-Consequences:

1.) salt washing - severe dehydration = adrenal crisis

2.) virilizing type - increased fetal adrenal androgens

Front 10

Name the disorders of Renal aminoaciduria (aminoacidopahties)?

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1.) cystinuria

2.) Harnup Syndrome

Front 11

renal aminoaciduria?

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-increase urine amino acid due to defiency in active transport molecule that is respo. for reabsorbing amino acids from PCT.

-Serum conc = N to decresed

Ex: Cystinuria & Hartnup Syndrome

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Cystinuria?

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-lack of transport to reabsorb COLA (cystenine, ornithine, lysine, arginine)

-Excess of poor-soluble CYSTEINE in urine = renal calculi
-Lab Finding:colorless, hexagonal cysteine crystals in acidic urine.

-Treatment: restrict diet, hydration, maintain pH 7.5, chelation & surgery. Goal is sulfrylsulfide bonds must be broken.

Front 13

Hartnup syndrome?

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-unable to reabsorb {neutral amino acids} from PCT due to deficient transport molecule.

-Symptoms: neurlogic, dermititis

-Treatment: don't consume amino acids, nicotenemide = neutralize amino acids

Front 14

Name the disorders of overflow aciduria ?

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1.) PKU

2.) Tyrosinemia

3.) Alkapotnuria

4.) Albinism

5.) MSUD (maple syrup urine disease)

6.) homocystinuria

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Overflow aciduria?

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-increase blood conc. due to defiency in metabolic pathway of amino acid.

-Increase conc. in urine due to overflow

ex: pku, tyrosinemia, alkapotnuria, albinism, MSUD, homocystunria

Front 16

PKU?

Back 16

-defiecient phenylalinine-hydroxylase which is required to convert (phenylalinine - tyrosine)
-increase concentration in plasma and urine = abnormal metabolites in urine = phenyl-lactic, phenyl- pyruvate, phenyl- acetic acid.

-musty odor (ketones)

-undiagnosed/untreated = development delay 1st year, followed by severe mental retardation & hypopigmenation .
Guthrie test

Front 17

Why is there hypopigmentation in PKU?

treatment for PKU?

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- phenylaline is a competitive inhibitor of enzyme tyrosinase, which is the enzyme that initiates the production of melanin.

-too much phenyalaine = block melanin

Treatment: eliminate phenylalanine from diet to prevent problem

Front 18

what is the new born screening performed on PKU calleD?

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Guthrie test

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what is the Guthrie test?

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-Spores B. subitilis agar defiecient of phenylalanine and a disk of b -2 thienylanine on media.

-B-2 thienylalinine inhibits strain cuz phenylalaine allows the organism to overcome media.

-Procedure: incubate blood soaked filter paper on agar overnight, and look for growth.

-Growth bacteria = excessive phen in pt's serum

-Initial results require confirmation by quantitative serum phe analysis > 6 mg/dL requires dietary restrictions.

Front 20

Women who have ceased dietary restriction of phd will give birth to infants that are already what?

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compromised & mentally retarded

Front 21

Women who have PKU must return to what prior to conception and throughout the pregnancy?

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restricted diets

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Tyrosinemia

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- type 1 tyrosinemia: FAA hydrolase

- type 2 tyrosinemia:tyrosine amino transferase

-elevated tyrosine in blood and urine

-enzyme defiency in metabolic pathway

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Alkapotnuria

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-1st inborn error of metabolism 1900's

-lack of homogentisic acid oxidase --> build up of homogentisic acid = dark blue or black deposits in cartilage.

-Urine = dark upon standing or addition of base (alkaline pH)

-phenalyine + tyrosine = homogentisic acid

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albinism

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-absence of tyrosinase, enzyme that converts tyrosine to melanin

-lack of pigment: poor eye sight, lack hair color, skin, eyes

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MSUD?

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-branched chain aminaciduria
-deficient enzyme (ketoacid decarboxylase) for the metabolism of (leucine, isoleucine & valine) [VIL]
-metabolite accumulate ketone deratives = odor of maple syrup in sweat, urine.

-Dietary restricitions = INEFFECTIVE

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Homocystinuria

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-deficient cystathione synthase def (converts homocystin to cystathione)
-Especially effects (METHIONE regeneration
-infants appear normal at birth but symptoms appear w/age = mental retardation, osteoporosis

-Treatment: folic acid and Vit. B 12, have low diet in homocystine & methionine.

Front 27

Name disorders that are Carbohydrate abnormalities?

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-Galactosemia
-GSD(glycogen storage disease)

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Galactosemia?

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-defiency enzyme UDP- galactose 1 phosphate to convert galactose to glucose --> side reactions cause accumulation of GALACTITOL.

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-Routine urinalysis of patients for Galactosemia?

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- < 2 yrs old include 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

-Early detection of galactosemia = removal of lactose & galactose from diet and prevent retardation, cirrhosis & cataract.

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GSD (glycogen storage disease)

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-enzyme defects & accumulation of glycogen in liver and skeletal muscle.

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Type 1:

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-defiency glucose 6- phosphatase
-glycogenolysis, hypoglycemia, growth retardation, ketosis, Lactic acidosis, hepatomegaly

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Type 2,5,7:

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-other enzyme defects
-milder symptoms
-increase glycogen (skeletal muscle)

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Type 3,6:

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liver forms of glycogen storage disease

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type 4:

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severe liver forms of glycogen storage disease

-skeletal & cardiac muscle disease

Front 35

Deficient enzymes are responsible for what?

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metabolizing diff. fatty acids

Front 36

Disorders of glycolipids?

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abnormal lipid storage which inhibits body's ability to utilize stored fat.

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Cystic fibrosis:

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-deficeint transmembrane protein= viscous secretion, lung disease, pancreatic insufficiency.
-deletion of delta 508 on phenylalanine.

Front 38

Screening test for Cystic Fibrosis?

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-Increase Cl Sweat test

-1st: inject pilocarpine (stimulate sweat glands) into skin

-2nd: collect 50-100 microL of sweat and measure Cl- conc

-3rd: calculate mmol/L sweat Cl-