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Flashcards in Metabolic Diagnostics/Disoders/NS Deck (33)
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3 Tiers of Lab Diagnosis for Metabolic Disorders

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


3 Categories of Tier Two Tests

Organic acids in urine
Amino acids in plasma
Acylcarnitine profile


3 Categories of Tier 3 Tests

Enzyme analysis
Molecular analyses
Function tests


Preparation for Metabolic Disorder Test

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


Traditional NBS Model

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


NBS Model by MS/MS

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


NBS Test/Treatment for Hypothyroidism (3)

TSH, if positive confirm w/ thyroid hormones
Treat w/ L-thyroxine


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

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


Diagnosis and 2 Treatments of CAH

17-OH Progesterone
Treat w/ mineralocorticoid and glucocorticoid


3 Treatments of of Classic PKU

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


3 Types of PKU from Defect in PAH Gene

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


Treatment of Biopterin Defects

Control phe levels w/ diet or BH4 and NT replacements


Maternal PKU

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


Maple Syrup Urine Disease 2 Treatments

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


Symptoms and Treatment of Biotinidase Deficiency

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


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

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


Galactosemia (untreated and treated)

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


8 Factors in Management of Inborn Errors of Metabolism

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


3 Basic Principles of Inborn Errors of Metabolism

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


Definition of Inborn Error

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


2 Types of Glycogen Storage Diseases (GSDs)

Type I: Von Gierke Disease
Type II: Pompe disease


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

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


Ornithine Transcarbamylse Deficiency (OTC) (4)

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


Coarse Faces

Sign of MPS


3 Classifications of MPS 1

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


Protein Levels in MPS 1

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


4 Big Symptoms for MPS I

Carpal tunnel
Umbilical/inguinal hernia
**Corneal clouding


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

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


Bone Marrow Transplantation for MPS I (2)

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


Sphingolipidoses 2 Shared Features

Always affect CNS/nervous tissue
Cherry-red spot in ophthalmological examination


Tay-Sachs Onset

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


3 Types of Gaucher Disease

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


3.2 Treatments of Type I Gaucher

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