Inborn Errors of Metabolism Flashcards
conditions to perform population screening
- 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
when most false negative newborn screenings
- preterm infants
- infants tested before 24 hours of age
- blood transfusion
disorders screened in Ohio
- hearing - otoacoustic emission testing
- congenital heart disease - pulse oximetry
- metabolic disorders
Big 7 diagnosis of hypoxemia
- hypoplastic left heart syndrome
- pulmonary atresia
- Tetralogy of Fallot
- total anomalous pulmonary venous return
- transposition of the great arteries
- tricuspid atresia
- truncus arteriosus
when newborn metabolics tested
24-48 hours of life
(after 24h because must have been fed)
what done if positive test
follow-up tests - don’t wait to tx symptoms
(false positives not rare)
hypoglycemia, hepatomegaly, lethargy
inability to break down glycogen
glycogen storage disease
(tx with frequent feedings)
liver failure, renal tubular dysfunction, cataracts
galactosemia
(withhold galactose w/in first week of life to prevent death)
S/s, Tx of amino acid disorders
- 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
normal at birth
developmental delay
seizures
microcephaly
musty odor to urine and skin
reduced melanin: light eyes and skin
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
failure to thrive
vomiting, diarrhea, often w/ blood
hepatomegaly
jaundice
irritability
cabbage-like odor
tyrosinemia
- inability to metabolize tyrosine
- Tx:
- Nitisinone- limits succinylacetone prod.
- restrict phenylalanine and tyrosine diet
- liver transplant
lens dislocation
osteoporosis
vascular events
death
mental retardation (approx. 50%)
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
ketosis and hyperglycinemia
vomiting, lethargy, coma
difficult to treat
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
urine and ear wax smell of maple syrup
most often in Pennsylvania Mennonites
depression of CNS, hypoglycemia, hypo/hypertonia alternating seizures
maple syrup urine disease
- cannot break down branched chain a.a. (Leu, Ile, Val)
- Tx:
- leucine (BCAA) restricted diet
- liver transplant ultimately
purpose of urea cycle
removes amonia from body
(product is urine - nontoxic and can be excreted)
growth retardation
combativeness, lethargy, seizures, coma
muscle weakness, hypertonia, tremors, ataxia
hepatomegaly
disorders of ammonia disposal
- Tx:
- reduce protein intake - reduce ammonia
- IV glucose to suppress catabolism
- hemodialysis/filtration to reduce NH4
interfere w/ ability to turn fat into energy
hypoglycemia, seizures, weakness
disorders of fatty acid metabolism
- Tx:
- frequent meals
- eat starches
common error in fatty acid metabolism
hypoglycemia, elevated liver enzymes, fatty infiltrate of liver
episodes occur with fasting
medium chain acyl CoA dehydrogenase deficiency
(MCAD deficiency)
- Tx:
- avoid medium chain fatty acids
- coconut/palm oil, dairy, fast foods
- no fasting
- avoid medium chain fatty acids
hypoglycemia
lethargy
muscle weakness
sudden death
hypoketotic, hypoglycemic encaphalopathy
risk of arrhythmias
carnitine deficiency
- carnitine crucial for transport of fatty acids into mitochondrion for metabolism
- Tx:
- 10% dextrose IV
- oral/IV carnitine supplement
muscle fatigue
ragged red fibers on muscle biopsy
pain, fatigue, m. myopathy, seizures, dev. delay, GI
mitochondrial disorders
- may only be expressed in certain tissues
- Tx:
- PT
- rest
- nutrition
- vitamin cofactors
- mitochondrial cocktail
- genetic manipulation- mother nucleus into donor egg
disorders diagnosed at birth
(newborn screening)
- endocrine
- congenital adrenal hyperplasia
- can’t synthesize cortisol
- primary congenital hypothyroidism
- low/absent thyroid hormone
- congenital adrenal hyperplasia
- 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
- biotinidase deficiency
what to screen for w/ seizures, encephalopathy
- hypoglycemia
- amino acid disorders
- fatty acid disorders
what to screen for w/ hepatomegaly, hepatic dz
- glycogen storage disease
- mucopolysaccharoidosis
- galactosmia, hereditary fructose intolerance
what to screen for w/ jaundice (too high/too long)
- any hepatic disease
- Crigler Najar disease
- Rotor and Dubin Johnson syndromes
what to screen for w/ metabolic acidosis
- organic acid disorders
- fatty acid disorders
- galactosemia
