deck 1

Question 1

Causes of hyperammonemia

Answer 1

1. urea cycle defect (most common cause of high ammonia) - encephalopathy, can get respiratory alkalosis, eventually can get metabolic alkalosis and acidosis, damages the brain quickly so need to diagnose quickly
2. organic acidemia (i.e. propionic acuduria) 30% of the severe neonatalhyper ammonia, blocked urea synthesis from deficiency of acetyl CoA and inhibition of NAGS by organic acids, usually have lactic acidosis at early stage (sometimes alkalosis from vomiting)
3. severe liver failure
4. transient hyperammonemia from PDA (neonates)
5. increased muscle activity:
   - assisted ventilation, RDS, after seizure (but shouldn’t be >180)

Question 2

What level of ammonia to be concerned about in term babies?

Answer 2

if >200 in term baby, strongly suspect metabolic disorder

Question 3

Kid with hyperammonemia and suspected metabolic disease. What investigations do you do?

Answer 3

1. stop intake of potentially toxic compounds (i.e. protein, fat, galactose, fructose)
2. insert IV and do blood samples:
   - lytes, glucose, CRP, CK, ALT, AST, creatinine, urea, uric acid, acid bas status, coags, ammonia, lactate
   - plasma sample for amino acids, acylcarnitines
   - urine for ketones, glucose, protein, pH (remember if ph >5 during acidosis suggests RTA which is associated with metabolic diseases)
3. start with 10% glucose 150 ml/kg/day

Question 4

You suspect a metabolic disorder and start a glucose infusion. Which cape of condition might it be harmful in?

Answer 4

May be harmful in mitochondrial disorders - especially pyruvate dehydrogenase deficiency, since high glucose supply may worsen the lactic acidosis
benefits outweigh the risks but need to check lactate and acid-base status regularly

Question 5

You have started your glucose infusion of D10 at 150 ml/kg/day (10 mg/kg/min) but keep getting low glucoses, suspect metabolic disorder, what diseases should you suspect?

Answer 5

may not be sufficient for d/o that are worsened by catabolism: organic acidurias or urea cycle defects

usually this level of glucose is okay for disorders of reduced fasting tolerance: glycogen storage d/o, MCAD deficiency

Question 6

neonate patient has hypoglycaemia (glucose 2.0) , what tests do you do in your critical sample and what do they tell you?

Answer 6

1. FFA and 3 hydroxybutyrate: if low, think of hyper insulin or hypo pit, if high think of fatty acid oxidation or ketogenesis defect
2. Actylcarnitines - diagnose most fatty acid oxidation disorders and organic acudurias
3. hormones - insulin and corisol
4. lactate-

Question 7

Causes of hypoglycaemia in neonate

Answer 7

in prems may not need to look that far - problems in adaptation, other non metabolic causes - sepsis, systemic illness, SGA< maternal diabetes
#1. hormonal - hyperinsulin/hypopit ->low concentrations of FFAs and ketones since don't have much lipolysis 
2. regulatory disturbances - hypoglycaemia with strong ketones (ketotic hypoglycaemia, glycogen storage disease type III, hypo pit after first year)
3. defect of fatty acid utilization (carnitine shuttle, fatty acid oxidation, ketogenesis) : hypoglycaemia, high FFAs, low ketones during lipid catabolism (should have more ketones when starving)
4. gluconeogenesis defects (glycogen storage disease I) - lactic acidosis, can have low or high ketones

Question 8

hyperammonia - investigations

Answer 8

1. Basic investigations (- lytes, glucose, CRP, CK, ALT, AST, creatinine, urea, uric acid, acid bas status, coags, ammonia, lactate
   - plasma sample for amino acids, acylcarnitines
   - urine for ketones, glucose, protein, pH (remember if ph >5 during acidosis suggests RTA which is associated with metabolic diseases)
2. amino acids in plasma and urine
3. organic acids and orotic acid in urine
4. acylcarnitine in dried blood spots

Question 9

Management of hyperammnonemia:

Answer 9

start ASAP
Extra-corporeal detox if NH3>500
Principles
1. stop protein intake, reduce catabolism
2. remove ammonia - drugs, EC detox
3. replace urea cycle intermediates with arginine or citrulline, support mitochondrial metabolism with carnitine in organic acidurias
4. support urinary ammonia excretion by generous fluid intake, consider forced diuresis

First infusion: 
glucose 10 mg/kg/min
arginine
Na-benzoate 9some controversy about this one - provide alternate pathways 
Carnitine

check glucose, add insulin if needed
check ammonia after 2 hours

Question 10

What are some renal causes of metabolic acidosis?

Answer 10

1. rental tubular acidosis
2. Fancony - Bickel disease - glycogenosis type XI from Gult2 deficiency, causes RTA, aminoaciduria, phosphaturia, glycosuria, fasting hypoglycaemia
3. low syndrome - RTA, cataracts, glaucoma, hypotonia
4. osteopetrosis - RTA, bone changes
5. cystinosis

And accompanying feature of metabolic diseases which can affect the kidney:

• tyrosinemia
• hereditary fructose intolerance
• glycogen storage disease type I
• mitochondrial disorders
• methylmalonic aciduria (chronic renal damage)

Question 11

ketonuria in the neonate is often indicative of what?

Answer 11

primary metabolic d/o

Question 12

ddx of ketosis

Answer 12

mitochondrial diseases

i.e. organic acidurias, resp chain disorders