Inborn Errors of Metabolism

Question 1

conditions to perform population screening

Answer 1

• serious conditions
• reliable test w/ low false negatives
• condition has effective tx
• early dx and tx improves outcome
• simple and inexpensive
• timely results
• definitive follow-up test available

Question 2

when most false negative newborn screenings

Answer 2

• preterm infants
• infants tested before 24 hours of age
• blood transfusion

Question 3

disorders screened in Ohio

Answer 3

• hearing - otoacoustic emission testing
• congenital heart disease - pulse oximetry
• metabolic disorders

Question 4

Big 7 diagnosis of hypoxemia

Answer 4

• hypoplastic left heart syndrome
• pulmonary atresia
• Tetralogy of Fallot
• total anomalous pulmonary venous return
• transposition of the great arteries
• tricuspid atresia
• truncus arteriosus

Question 5

when newborn metabolics tested

Answer 5

24-48 hours of life

(after 24h because must have been fed)

Question 6

what done if positive test

Answer 6

follow-up tests - don’t wait to tx symptoms

(false positives not rare)

Question 7

hypoglycemia, hepatomegaly, lethargy

inability to break down glycogen

Answer 7

glycogen storage disease

(tx with frequent feedings)

Question 8

liver failure, renal tubular dysfunction, cataracts

Answer 8

galactosemia

(withhold galactose w/in first week of life to prevent death)

Question 9

S/s, Tx of amino acid disorders

Answer 9

• normal at birth but fail developmental milestones
• seizures
• microcephaly
• progressive impairment of cerebral function
• musty/mousy odor
• tendency towards hypopigmentation/eczema
• Tx: avoid ingesting the amino acid

Question 10

normal at birth

developmental delay

seizures

microcephaly

musty odor to urine and skin

reduced melanin: light eyes and skin

Answer 10

phenylketonuria

• phenylalanine cannot be catabolized to tyrosine
• exclude phenylalanine from diet
  
  • no meats, dairy, beans, nuts, eggs, wheat
  • no diet soda
  • fruits, vegetables, sugars, low-protein foods okay

Question 11

failure to thrive

vomiting, diarrhea, often w/ blood

hepatomegaly

jaundice

irritability

cabbage-like odor

Answer 11

tyrosinemia

• inability to metabolize tyrosine
• Tx:
  
  • Nitisinone- limits succinylacetone prod.
  • restrict phenylalanine and tyrosine diet
  • liver transplant

Question 12

lens dislocation

osteoporosis

vascular events

death

mental retardation (approx. 50%)

Answer 12

homocystinuria

• cystathione B synthase deficiency - cannot metabolize methionine
• homocysteine/methionine accumulate in blood and urine- drives pathway backwards
• Tx:
  
  • pyridoxine- increases CBS activity
  • methionine restricted diet and folate supplements

Question 13

ketosis and hyperglycinemia

vomiting, lethargy, coma

difficult to treat

Answer 13

organic acid disorders

• inability to catabolize amino acids - accumulation
• urinary excretion of large amounts of organic acids
• proprionic acidemia, methylmalonic acidemia, isovaleric acidemia, maple syrup urine disease

Question 14

urine and ear wax smell of maple syrup

most often in Pennsylvania Mennonites

depression of CNS, hypoglycemia, hypo/hypertonia alternating seizures

Answer 14

maple syrup urine disease

• cannot break down branched chain a.a. (Leu, Ile, Val)
• Tx:
  
  • leucine (BCAA) restricted diet
  • liver transplant ultimately

Question 15

purpose of urea cycle

Answer 15

removes amonia from body

(product is urine - nontoxic and can be excreted)

Question 16

growth retardation

combativeness, lethargy, seizures, coma

muscle weakness, hypertonia, tremors, ataxia

hepatomegaly

Answer 16

disorders of ammonia disposal

• Tx:
  
  • reduce protein intake - reduce ammonia
  • IV glucose to suppress catabolism
  • hemodialysis/filtration to reduce NH4

Question 17

interfere w/ ability to turn fat into energy

hypoglycemia, seizures, weakness

Answer 17

disorders of fatty acid metabolism

• Tx:
  
  • frequent meals
  • eat starches

Question 18

common error in fatty acid metabolism

hypoglycemia, elevated liver enzymes, fatty infiltrate of liver

episodes occur with fasting

Answer 18

medium chain acyl CoA dehydrogenase deficiency

(MCAD deficiency)

• Tx:
  
  • avoid medium chain fatty acids
    
    • coconut/palm oil, dairy, fast foods
  • no fasting

Question 19

hypoglycemia

lethargy

muscle weakness

sudden death

hypoketotic, hypoglycemic encaphalopathy

risk of arrhythmias

Answer 19

carnitine deficiency

• carnitine crucial for transport of fatty acids into mitochondrion for metabolism
• Tx:
  
  • 10% dextrose IV
  • oral/IV carnitine supplement

Question 20

muscle fatigue

ragged red fibers on muscle biopsy

pain, fatigue, m. myopathy, seizures, dev. delay, GI

Answer 20

mitochondrial disorders

• may only be expressed in certain tissues
• Tx:
  
  • PT
  • rest
  • nutrition
  • vitamin cofactors
  • mitochondrial cocktail
  • genetic manipulation- mother nucleus into donor egg

Question 21

disorders diagnosed at birth

(newborn screening)

Answer 21

• endocrine
  
  • congenital adrenal hyperplasia
    
    • can’t synthesize cortisol
  • primary congenital hypothyroidism
    
    • low/absent thyroid hormone
• other
  
  • biotinidase deficiency
    
    • inability to use vitamin biotin
  • cystic fibrosis
    
    • 40 separate gene mutations scrn’d
  • severe combined immunodeficiency
    
    • can’t develop mature B and T cells
  • hemoglobinopathies
    
    • most freq. positive test
    • sickle cell, SC dz, B thalassemia

Question 22

what to screen for w/ seizures, encephalopathy

Answer 22

• hypoglycemia
• amino acid disorders
• fatty acid disorders

Question 23

what to screen for w/ hepatomegaly, hepatic dz

Answer 23

• glycogen storage disease
• mucopolysaccharoidosis
• galactosmia, hereditary fructose intolerance

Question 24

what to screen for w/ jaundice (too high/too long)

Answer 24

• any hepatic disease
• Crigler Najar disease
• Rotor and Dubin Johnson syndromes

Question 25

what to screen for w/ metabolic acidosis

Answer 25

• organic acid disorders
• fatty acid disorders
• galactosemia