inborn errors in metabolism Flashcards
When it is ok to do Mass screening for illnesses? (7)
- Dz is common and serious enough to be worth it
- There is a pre-Sx impact (knowing would change the course of the dz)
- ID of risk does not result in discrimination
- Early Tx is available
- Test has specificity (low false +) and sensitivity (low false -)
- Available for everyone
- Cost/benefit
Suspect an inborn error of metabolism when? (8)
- Sx with changes in diet
- Development of child decreases (all declines need a full work-up)
- Specific food aversions
- FH retardation or unexplained deaths
- Appear sepsis
- Recurrent hypoglycemia
- Neuro Sx don’t follow patterns
- Unexplained acidosis
D/o of toxic accumulation (precursers that cause toxicity) (3)
a. Protein metabolism d/o
b. Carb intolerance
c. Lysosomal storage d/o
2 Categories of inborn error of metabolism?
- D/o of toxic accumulation (precursers that cause toxicity)
- D/o of E production/utilization
D/o of E production/utilization (4)
a. Fatty acid oxidation defects
b. Carb utilization or production d/o
c. Mitochondrial d/o
d. Perioxisomal d/o
Phenylketonuria
- Amino acid metabolism d/o (hyperphenylalaninemia) (enzyme d/o)
- Autosomal recessive
Presentation of Phenylketonuria
o Severe MR
o Hyperactivity
o Seizures
o Light complexion, blond hair, eczema
Treatment of Phenylketonuria
o Emilination diet in 1st mo of life
o Phenylalanine LOW diets to allow normal growth
o Regulate mother before and during birth
Galactosemia
- Near total deficiency of galactose 1-p uridyltransferase (enzyme)
- Autosomal recessive
Presentation of Galactosemia
o Neonate vomiting, jaundice, hepatomegaly, rapid liver insufficiency after the initiation of milk feeding
o Progressive cirrhosis
Treatment of Galactosemia
o Prompt galactose-free diet
• Liver Dz prognosis is good
• Speech, ovarian, language prognosis not so good
o Ca2+ supplements
Maple Syrup Urine Disease
- D/t deficiency of decarboxylation enzyme for keto acids (leucine, isoleucine, valine)
- Autosomal recessive
Presentation of Maple Syrup Urine Disease
o Normal at birth
o One week later: feeding difficulties, coma, seizures
o Most die in 1st mo w/no diet restriction
Treatment of Maple Syrup Urine Disease
o Dietary leucine restriction
o Catabolism avoidance (don’t diet)
Homocystinuria
- Deficiency of CBS (enzyme)
- Autosomal recessive
- Untreated → 50% MR
Presentation of Homocystinuria
o Looks like Marfans dz
o Arachnodactyly (spider fingers)
o Osteoporosis and dislocated lenses
o Thromboembolic phenomena (OCP risk later)
Treatment of Homocystinuria
o Lg oral doses of pyridoxine
o Non-responders Tx with methionine restrictions
o Avoidance of OCPs (coag risk)
Nonketotic Hyperglycemia
- Deficiency of glycine enzyme
- Autosomal recessive
- Most develop MR and seizures
Presentation of Nonketotic Hyperglycemia
o Hypotonia, lethargy
o Developmental delays, chorea later
Treatment for Nonketotic Hyperglycemia
o Sodium benzoate (preservative) and dextromethorphan or ketamine
Organic Acidemias
- Amino/fatty acid metabolism d/o which causes accumulation of nonamino organic acids accumulate in serum and urine
- Autosomal recessive
Fatty acid oxidation disorder
• Difficulty breaking down long fatty acid chains • Presentation o Reye-like episodes o HypOketotic, hypOglycemia o HypERammonemia o Hepatomegaly, encephalopathy
Treatment for Fatty acid oxidation disorder
o Avoid prolonged fasting (to prevent hypOglycemia)
Smith-Lemli-Opitz Syndrome
- Autosomal recessive
* Enzyme deficiency
