Metabolic Disorders Flashcards
1
Q
PKU
A
- MOST COMMON amino aciopathy (1/10,000-15,000)
- AR mutations in PAH
- untreated: ID, seizures, musty odor, psych
- inc. phenylalanine, dec. tyrosine
- treated: generally unaffected
- dietary protein restriction
- Kuvan works for some
2
Q
Tyrosinemia type I
A
- amino aciopathy
- AR mutations in FAH
- more common in Quebec (1/16,000)
- untreated: liver failure in infancy, kidney dysfxn, growth failure, rickets, neuro crises, death <10y, rotton eggs odor
- increased phenylalanine and tyrosine in plasma, increased succinylacetone in urine
treated: inc. risk hepatocellular carcinoma, corneal cysts, normal growth, increased liver fxn - drug treatment NTBC, dietary protein restriction, manage liver disease
3
Q
Homocytinuria
A
- amino aciopathy
- AR mutations in CBS
- more common in Qatar (1/1,800)
- untreated: ID, marfanoid, ectopia lentis (down), thromboembolism, neuro sequelae
- increased homocystine and methionine
- treated: inc. risk for thromboembolism, risk of ectopia lentic, normal growth and intelligence
- supplement with B6, folate, B12, dietary protein restriction, avoid OCPs
4
Q
MSUD
A
- amino aciopathy
- AR mutations in BCKDHA (45%), BCKDHB (35%), DBT (20%)
- more common in Mennonites
- newborn metabolic crisis: irritability, feeding and resp issues, opisthotonas
- reduced IQ, movement disorders, risk of depression, ADHD, and anxiety
- increased BCAAs (leucine, isoleucine, valine)
- dietary protein restriction (most aggressive when sick)
5
Q
Amino acidopathies presentation
A
- chronic and progressive
- usually no neonatal crisis (except MSUD)
- all AR
- symptoms develop slowly
6
Q
Urea cycle defects
A
Neonatal presentation: - increased ammonia, encephalopathy, resp. alkalosis: - seizure, coma, death - resembles sepsis but normal glucose - onset 24-72hrs of life Childhood and adult presentation - infections, neuro involvement, psych issues - PREVENT CATABOLISM - SUPPLEMENT WITH ARGININE (unless ARG) LIVER TRANSPLANT = CURE
7
Q
CPS deficiency
A
- urea cycle defect
- AR mutations in CPS1
- plasma AAs: low citrulline and arginine
8
Q
OTC deficiency
A
- MOST COMMON urea cycle defect
- XL mutations in OTC
- plasma AAs: low citrulline and arginine
- high urinary orotic acid
- 10-15% CARRIER females symptomatic
9
Q
ASS deficiency/Citrullinemia
A
- urea cycle defect
- AR mutations in ASS1
- super inc. citrulline, dec. arginine
10
Q
ASL deficiency
A
- urea cycle defect
- AR mutations in ASL
- inc. citrulline and arginosuccinate, dec. arginine
- variable
11
Q
ARG deficiency
A
- urea cycle defect
- AR mutations in ARG1
- onset 1-3y: progressive spasticity, psychomotor retardation, feeding issues, DD, seizures
- increased arginine
12
Q
Organic Acidurias
A
- high risk of decompensation prior to NBS results
- prevent catabolism!
- acute presentation: toxic encephalopathy, dec. feeding, poor tone, seizures, irritability, lethargy -> coma
- all AR
- treat with carnitine supplementation
13
Q
Propionic acidemia
A
- organic aciduria
- AR mutations in PCCA, PCCB
- cannot metabolize: isoleucine, valine, threonine, methionine
- neonatal fast breathing
- cardiomyopathy
- pancreatitis
14
Q
Glutaric Acidemia
A
- MOST COMMON organic aciduria (1/30-40,000)
- AR: GCDH
- up to 1/300 Amish
- metabolic crisis after 2 months
- severe movement disorder: spasticity/dystonia (from glutaric acidemia)
- macrocephaly
- treat: low lysine diet
- 30-40% have neuro impariment w/ treatment
15
Q
Methlymalonic aciduria
A
- organic aciduria
- AR: MUT (genotype/phenotype…22% have limited activity)
- looks like PA in severe genotype
- very high MMA
- treatment: DPR, B12 injections, prophylactic antiboitics
16
Q
Isovaleric Aciduria
A
- organic aciduria
- AR: IVD
- similar to PA and MMA neonatal crisis, BUT fewer longterm complications
- “sweaty feet odor”
- treatment: low leucine
17
Q
Metabolic conditions w/ psychiatric findings
A
PKU, Galactosima, MCADD, ASA, Citrullinemia (ASD), homocystinuria
18
Q
Fatty Acid Oxidation Disorders
A
- causes sudden infant death
- avoid fasting!
- low fat diet w/ fatty acid supplementation
- cornstarch
19
Q
SCAD
A
- not a disorder…in vast majority
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