Metabolics

Question 1

PKU

Answer 1

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

Question 2

Tyrosinemia Type 1

Answer 2

• presents as decompensation with acute liver failure
• reversible if caught early and treated!

Question 3

Presentation of Organic Acid Disorders

Answer 3

• 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)

Question 4

Presentation of Urea Cycle Defects

Answer 4

• feeding intolerance, vomiting, lethargy, progression to coma
• respiratory alkalosis (ammonia is a respiratory stimulus)
• hyperammonemia (REPEAT IT FIRST)

Question 5

Examples of UCD

Answer 5

• ornithine transcarmabylase (OTC) - most common
• citrullinemia
• argininosuccinate lyase
• arginase

Question 6

Metabolic disorders with hyperammonemia

Answer 6

• urea cycle defects (respiratory alkalosis)
• organic acid disorders (metabolic acidosis)

Question 7

Presentation of FAOD

Answer 7

• presentation during times of fasting
• hypoketotic hypoglycemia (younger)
• rhabdomyolysis (older)
• cardiomyopathy/arrhythmia
• hepatoencephalopathy
• secondary carnitine deficiency

Question 8

Management of FAOD

Answer 8

• restrict fat in diet (not in MCAD)
• **avoidance of fasting!! (DO THIS FIRST WHILE INVESTIGATING)

Question 9

Presentation of Hereditary Fructose Intolerance

Answer 9

• presents at 4-6 months with intro of solids
• liver failure, coagulopathy, hypoglycemia
• fructose in urine!

Question 10

Presentation of Galactosemia

Answer 10

• presentation in 1st 10 days of life
• unconjugated hyperbili and poor feeding –> conjugated hyperbili, coagulopathy and liver failure
• cataracts
• E. coli sepsis

Question 11

Long term complications in galactosemia

Answer 11

• cataracts (reversible if picked up in first 2 months)
• speech apraxia
• premature ovarian failure
• ataxia
  Other complications are not reversible

Question 12

Which metabolic disorder is breast milk contraindicated in?

Answer 12

Galactosemia!
Needs soy based formula and long-term avoidance of dairy products

Question 13

Presentation of Glycogen Storage Disorders

Answer 13

*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

Question 14

Basic treatment of small molecule IEM

Answer 14

• 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)

Question 15

Specific treatment of Organic Acid Disorders

Answer 15

• 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)

Question 16

Treatment of hyperammonemia

Answer 16

• Stop protein
• D10W + lipids (promoted anabolism)
• remove ammonia (dialysis, scavengers)
• deficient substrates and co-factors (arginine, citrulline, carnitine, carglumic acid)

Question 17

Treatment of GSD

Answer 17

• avoid hypoglycemia - frequent feeds, corn starch
• restrict fructose and galactose
• vitamin supplementation
  *long term risk of liver adenomas

Question 18

Investigations for IEM

Answer 18

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)

Question 19

Clinical features of lysosomal storage disorders

Answer 19

• coarse facial features
• HSM
• hypertrophic cardiomyopathy
• CNS - regression, spasticity, ataxia
• Heme involvement
• Cherry red spots, corneal clouding
• dysotosis multiplex

Question 20

Investigations for lysosomal storage disorders

Answer 20

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

Question 21

Treatment of lysosomal storage diseases

Answer 21

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

Question 22

Organic Acid Disorders

Answer 22

Question 23

Urea Cycle Disorders

Answer 23

Question 24

Fatty Acid Oxidation Disorders

Answer 24

Question 25

Mitochondrial disorders

Answer 25