Metabolic Diagnostics/Disoders/NS

Question 1

3 Tiers of Lab Diagnosis for Metabolic Disorders

Answer 1

1st Tier - Basic analyses available at all hospitals on emergency basis
2nd Tier - analyses typically available only at reference laboratories
3rd Tier - specific enzyme analyses/DNA testing

Question 2

3 Categories of Tier Two Tests

Answer 2

Organic acids in urine
Amino acids in plasma
Acylcarnitine profile

Question 3

3 Categories of Tier 3 Tests

Answer 3

Enzyme analysis
Molecular analyses
Function tests

Question 4

Preparation for Metabolic Disorder Test

Answer 4

Newborn needs to eat for at least 24 hrs before so metabolite can build up and such

Question 5

Traditional NBS Model

Answer 5

Simple - 1 disease/1 test/1 marker/1 cutoff

Question 6

NBS Model by MS/MS

Answer 6

Mass spec allows for complex testing of multiple conditions w/ many markers and cutoffs (can also pick up a lot of milder versions/conditions)

Question 7

NBS Test/Treatment for Hypothyroidism (3)

Answer 7

TSH, if positive confirm w/ thyroid hormones

Treat w/ L-thyroxine

Question 8

Most Common Congenital Adrenal Hyperplasia (and presentation in the sexes)

Answer 8

95% are deficiencies of 21-hydroxylase
Affected females often have ambiguous or completely masculinized external genitalia
Affected males may only have subtle hyperpigmentation of genitalia

Question 9

Diagnosis and 2 Treatments of CAH

Answer 9

17-OH Progesterone

Treat w/ mineralocorticoid and glucocorticoid

Question 10

3 Treatments of of Classic PKU

Answer 10

Restrict precursors (phe)
Add deficient products (tyr)
Provide pharmacological doses of vitamin precursors of active cofactors (BH4)

Question 11

3 Types of PKU from Defect in PAH Gene

Answer 11

Classic PKU - Phe concentrations > 1200 micromol/L
Variant PKU - 600-1200
Non PKU Hyperphenylalalinemia - 150-600, might not treat

Question 12

Treatment of Biopterin Defects

Answer 12

Control phe levels w/ diet or BH4 and NT replacements

Question 13

Maternal PKU

Answer 13

Most be SUPER managed before pregnancy, else child may have microcephy/retardation/malformation

Question 14

Maple Syrup Urine Disease 2 Treatments

Answer 14

Diet and avoid conditions that increase catabolism (fever, dehydration)

Question 15

Symptoms and Treatment of Biotinidase Deficiency

Answer 15

Developmental/neurological delay, as well as eczema and hair loss
Easiest to treat: biotin

Question 16

MCAD (what it is, what it causes/how it’s found, common causative gene, and treatments) (5.3)

Answer 16

Medium-chain acyl-coenzyme A Dehydrogenase deficiency
Once 3-24 mos start sleeping longer, longer fasts trigger hypoglycemia and a bunch of other shit
Find urine organic acids
ACADM is common mut
Treat w/ frequent feeds of glucose and carnitine, restrict precursors, and avoid catabolism

Question 17

Galactosemia (untreated and treated)

Answer 17

Untreated - fata from Gram - sepsis or hepatic renal failure
Treated - usually works, but sometimes still have learning/motor disabilities and women at increased risk for ovarian cancer

Question 18

8 Factors in Management of Inborn Errors of Metabolism

Answer 18

Restrict precursors or substrates
Add deficient products
Add vitamin precursors for active cofactors
Provide alternate pathways
Avoid environmental toxins
Induce enzyme production
Provide enzyme replaceent
Transplant unaffected organ/stem cell

Question 19

3 Basic Principles of Inborn Errors of Metabolism

Answer 19

1. Chemical individuality of humans
2. Genes (units of heredity) have a specific chemical effect on the body
3. These differences can be measured by chemical reactions

Question 20

Definition of Inborn Error

Answer 20

A biochemical disorder due to a genetically determined, specific, qualitative, and/or quantitative defect in a functioning protein molecule

Question 21

2 Types of Glycogen Storage Diseases (GSDs)

Answer 21

Type I: Von Gierke Disease

Type II: Pompe disease

Question 22

Urea Cycle Defects (problem and presentation, and 4 treatments)

Answer 22

Inability to clear ammonia
Stop eating after 2-3 days and may go into coma
Administer arginine, sodium benzoate, sodium phenylbutyrate, and protein restriction

Question 23

Ornithine Transcarbamylse Deficiency (OTC) (4)

Answer 23

X-linked
Most frequent urea cycle defect
Causes buildup of ornithine and deficiency of citrulline
Severe lethal hyperammonemia if untreated in males, females can die from minor infection

Question 24

Coarse Faces

Answer 24

Sign of MPS

Question 25

3 Classifications of MPS 1

Answer 25

Scheie - least severe
Hurler-Scheie - middle
Hurler: Most severe, involves CNS

Question 26

Protein Levels in MPS 1

Answer 26

Cases across whole spectrum typically have <1% of normal enzyme levels

Question 27

4 Big Symptoms for MPS I

Answer 27

Carpal tunnel
Umbilical/inguinal hernia
Hepatosplenomegaly
**Corneal clouding

Question 28

Enzyme Replacement Therapy (ERT) for MPS I (4 + drug nae)

Answer 28

Reduces lysosomal storage of GAGs
Requires ability of recombinant enzymes to enter cells/have mannose-6-P tag for processing to lysosome
But doesn’t cross BBB so won’t help eyes or brain
Aldurazyme is drug

Question 29

Bone Marrow Transplantation for MPS I (2)

Answer 29

Helps symptoms except for skeletal and cognitive impairment suffered prior
Increases risk of other infections n shit

Question 30

Sphingolipidoses 2 Shared Features

Answer 30

Always affect CNS/nervous tissue

Cherry-red spot in ophthalmological examination

Question 31

Tay-Sachs Onset

Answer 31

6-12 months by slowing development, seizures, and cherry red spot

Question 32

3 Types of Gaucher Disease

Answer 32

Type 1 - nonneuropathic (no CNS involvement)
Type 2 (acute neuronopathic) - CNS involvement
Type 3 (chronic neuronopathic) - milder CNS involvement

Question 33

3.2 Treatments of Type I Gaucher

Answer 33

Supportive care - analgesics/orthopedic procedures
ERT - effective in only this type
Substrate Inhibition Therapy