Metabolics Flashcards
PKU
Deficiency of phenylalanine hydroxylase
- progressive developmental delay and neurologic injury
- positive newborn screen
- Restriction of phenylalanine in the diet + formula (low phenlyalanine and tyrosine supplementation)
NOT a contraindication to breastfeeding
Tyrosinemia Type 1
- presents as decompensation with acute liver failure
- reversible if caught early and treated!
Presentation of Organic Acid Disorders
- feeding intolerance, vomiting, lethargy, progression to coma
- metabolic acidosis + hyperammonia (due to accumulation of organic acids and inhibition of UC)
- lactic acidosis + elevated ketones (due to energy deficiency)
Presentation of Urea Cycle Defects
- feeding intolerance, vomiting, lethargy, progression to coma
- respiratory alkalosis (ammonia is a respiratory stimulus)
- hyperammonemia (REPEAT IT FIRST)
Examples of UCD
- ornithine transcarmabylase (OTC) - most common
- citrullinemia
- argininosuccinate lyase
- arginase
Metabolic disorders with hyperammonemia
- urea cycle defects (respiratory alkalosis)
- organic acid disorders (metabolic acidosis)
Presentation of FAOD
- presentation during times of fasting
- hypoketotic hypoglycemia (younger)
- rhabdomyolysis (older)
- cardiomyopathy/arrhythmia
- hepatoencephalopathy
- secondary carnitine deficiency
Management of FAOD
- restrict fat in diet (not in MCAD)
- **avoidance of fasting!! (DO THIS FIRST WHILE INVESTIGATING)
Presentation of Hereditary Fructose Intolerance
- presents at 4-6 months with intro of solids
- liver failure, coagulopathy, hypoglycemia
- fructose in urine!
Presentation of Galactosemia
- presentation in 1st 10 days of life
- unconjugated hyperbili and poor feeding –> conjugated hyperbili, coagulopathy and liver failure
- cataracts
- E. coli sepsis
Long term complications in galactosemia
- cataracts (reversible if picked up in first 2 months)
- speech apraxia
- premature ovarian failure
- ataxia
Other complications are not reversible
Which metabolic disorder is breast milk contraindicated in?
Galactosemia!
Needs soy based formula and long-term avoidance of dairy products
Presentation of Glycogen Storage Disorders
*Due to inability to break down glycogen into glucose
- hypoglycemia with hepatomegaly (not in liver failure)
- lactic acidosis
- high triglycerides
- high urate
*at risk of hepatoblastoma
Basic treatment of small molecule IEM
- Stop all intake (NPO)
- promote anabolism with energy (D10W + electrolytes +/- lipids (if not a FAOD)
- investigations/consults
- disease specific treatment (dietary restriction and supplementation of missing substrate)
Specific treatment of Organic Acid Disorders
- IV carnitine (deficiency due to binding and excretion of accumulating organic acids)
- restriction of specific amino acids and specialized formula/natural protein
*not as good as amino acid disorders due to wider spectrum, so outcomes not as good)
Treatment of hyperammonemia
- Stop protein
- D10W + lipids (promoted anabolism)
- remove ammonia (dialysis, scavengers)
- deficient substrates and co-factors (arginine, citrulline, carnitine, carglumic acid)
Treatment of GSD
- avoid hypoglycemia - frequent feeds, corn starch
- restrict fructose and galactose
- vitamin supplementation
*long term risk of liver adenomas
Investigations for IEM
BASIC
- blood gas and lactate
- electrolytes
- glucose
- CBC
- liver function and enzymes
- creatinine
- ammonia (UCD)
- CK (FAOD - rhabdo)
- urine dipstick for ketones
SPECIALIZED
- plasma amino acids (diagnostic of amino acid disorders and UCD)
- plasma acylcarnitine (diagnostic of FAOD, suggestive of OAD)
- carnitine (do with acylcarnitine)
- galactosemia screen
- urine sugar ID
- urine organic acids (diagnostic of OAD, suggestive of FAOD)
- urate + triglycerides (GSD)
Clinical features of lysosomal storage disorders
- coarse facial features
- HSM
- hypertrophic cardiomyopathy
- CNS - regression, spasticity, ataxia
- Heme involvement
- Cherry red spots, corneal clouding
- dysotosis multiplex
Investigations for lysosomal storage disorders
SCREENING
- vacuolated lymphocytes on PBS
- urine: MPS screen (GAGs) and oligosaccaride screen)
- skin biopsy for storage material in lysosomes
DIAGNOSTIC
- enzyme analysis
- molecular analysis
- plasma oxysterol
- urine sulfatides
Treatment of lysosomal storage diseases
Enzyme replacement therapy
- does not cross BBB
- does not alter MSK issues
- works for heart, liver, spleen, lungs
Substrate Reduction Therapy
- need some residual enzyme that can work to finish the rest of the substrate
- crosses the BBB
- reach equilibrium between synthesis and degradation
HSCT
- not curative
- most effective in MPS I and adrenoleukodystrophy (peroxisomal)
- improved visceral symptoms, not bone
Organic Acid Disorders
Urea Cycle Disorders
Fatty Acid Oxidation Disorders
Mitochondrial disorders
