Inborn Errors Of Metabolism I

Front 1

Amino Acid D/O

Back 1

1. PKU
2. tyrosinase-related albinism
3. homocystinuria
4. nonketoti hyperglycinemia
5. MSUD

Front 2

PKU

Back 2

1. defect phenylalanine hydroxylase (Phe to Tyr)
2. normal at birth
3. high Phe = brain damage, low Tyr = low NT and hypopigmentation
4. Musty odor
5. Heel stick: newborn screening
6. Tx: low Phe diet
7. mom with PKU must adhere diet prior and during pregnancy

Front 3

Tyrosinase-related albinism

Back 3

1. defect in tyrosinase (Tyr to melanin)
2. defect in P-gene
3. melanosmal defect
- locus heterogeniety causing lack melanin
- melanin need ocular development prenatally

Front 4

homocystinuria

Back 4

1. block at cystathionine synthase (homocystein to cystathionine)
2. block at re-methylation (homocystein to methionine) due missing Betaine/B12/folate
3. cystein becomes essential because no longer recycled methionine no longer donates methyl group to SAM
4. MR, marfanoid habitus, thrombosis often cause of death

Front 5

nonketotic hyperglycinemia

Back 5

1. defect metabolism glycine to NH3 and CO2
2. appears in 1st 24h unlike most AA d/o
3. hypotonia, encephalopathy, prenatal seizures, burst suppression EEG (high brain activity w/periods decreased activity)
4. EEG and elevated CSF/plasma glycine ration are diagnostic
5. tx: benzoate (reduce gly), dextromethorphan (SA) - poor prognosis

Front 6

MSUD

Back 6

1. failure metabolize branch chain AAs Val, Iso, and especially Leu needed for TCA cycle intermediates
2. newborn lethagic, poor feeder (like UCD), metabolic acidosis, and maple syrup odor
3. newborn screening: increased Leu
4. Tx: leu-free formula and if prior neuro symptoms than good prognosis
5. once leu levels decline can add back to diet because is essential AA

Front 7

Urea Cycle D/O

Back 7

1. inability to excrete waste nitrogen or synthesize arginine
2. ornithine transcarbamylase def - x linked, most common, female carriers present later in life (meat avoidance + vomiting)
3. onset 24h w/irritability, feeding problems, and labored breathing due NH3
4. initial labs: resp alkalosis and hyperammonemia
5. confirmatory labs for OTC: abscence of citrulline and elevated orotic acid
6. tx: low protein diet and hemodialysis/medication for elevated NH3

Front 8

Organic acidemias

Back 8

1. propionyl CoA metabolism - propionic acidemia and methylmalonic acidemia
2. isovaleric acidemia
3. glutaric acidemia type 1
- defects in conversion of OA to TCA intermediates
- metabolic acidosis

Front 9

propionic acidemia

Back 9

1. propionyl CoA cannot break down methylmalonyl CoA
2. biotin is cofactor
3. neonatal coma

Front 10

MMA

Back 10

1. methylamonly CoA cannot break down to Succinyl Coa
2. B12 is cofactor or due Cobalamin C d/o (common LA and will also have homocystinuria)
3. developmental delay, lethargic, thrombosis, marfan0like - similar presenation homocysteinuria
4. Dx: elevated urine MMA, low plasma Met, low B12
5. Tx: B12 SubQ injectinos for Cobalamin C type, consume regular diet

Front 11

isovaleric acidemia

Back 11

1. sweaty foot odor

Front 12

glutaric acidemia type 1

Back 12

1. dystonic movements late in infancy
2. macrocephaly and abnormal MRI
3. newborn screen for Dx
4. Tx: start neonatally and have normal growth and developmetn
5. w/in viral illness have increased risk metabolic encephalopathy

Front 13

lab dx for all OA

Back 13

1. metabolic acidosis (low bicarb)
2. increased anion gap, normall <15
3. ketosis - ketonuria on UA
4. possibly elevated ammonia
6. 2* carnitine deficiency

Front 14

UCD vs OA

Back 14

1. both lethargy and vomiting
2. UCD more hyperammonemia
3. ketoacidosis only in OA
4. resp alkalosis only UCD

Front 15

FAOD

Back 15

1. FA metabolism key path for adaption fasting
2. Lab for all FAOD: decrease glucose w/innappropriate decreased keton, confirm via acycarnitine profile
3. Tx: avoid fasting

Front 16

MCAD

Back 16

1. medium chain acyl-coa dehydrogenase deficiency
2. most common FAOD
3. asymptomatic until viral illness - poor apetite resulting in hypoglycemia and hypoketosis
4. newbron screen by acylcarnitine analysis - LCFA buildup attach carnintine generating fatty acyl carnitine

Front 17

Dz screened in newborns

Back 17

1. PKU
2. MSUD
3. glutaric acidemia type 1
4. MCAD