Metabolic Stuff for Dummies14 July, 2011 by: colinparker
Inborn Errors of Metabolism… OK, calm down, check your own pulse, and resist the urge to run away. Nobody likes biochemistry (OK, maybe one or two do like it), but fortunately we don’t need to learn the actual biochemical pathways in order to diagnose or manage these Congenital Metabolic Disorders.
Individually these conditions are rare, but as a group they are collectively common enough that we will encounter them in our Emergency Departments. Classifying these conditions is an ever-changing minefield, but understanding the basic principles is not too bad… especially with a bit of expert guidance from our guest brain.
Outline: Metabolic Stuff for Dummies
[AM] How common are Inborn Errors of Metabolism? ie how many kids under your care, in our little city of 1.7 million (state of 2.3 million)?
[cp] All usually caused by deficiency of a protein (usually enzyme) resulting in a metabolic roadblock.
3 groups of conditions based on mechanism of illness:
-acute accumulation of toxic small molecules
-chronic accumulation of large molecules
[kb] 1. Toxic intermediates esp amino acids / organic acids accumulate after birth (removed by placenta before birth) – present on day 2-5: acidosis, altered mental state, vomiting
OR may present later in times of physiologic stress, eg viral gastro in a toddler (IEM can go undiagnosed despite several episodes)
OR toxic molecules accumulate rapidly but cause damage slowly, therefore present after neonatal period eg PKU
[RR] 2. Disorders of energy metabolism eg ‘mitochondrial disorders’ – can present prenatally with IUGR/birth defects, because ATP cannot cross membranes. Usually Autosomal Recessive, poor prognosis, characterised by severe lactic acidosis, multisystem failure; commonly have seizures, cardiomyopathy, liver disease.
[cp] 3. Chronic accumulation of large molecules eg ‘lysosomal storage disorders’ – process of storage (mostly in connective tissues) begins prenatally because large molecules cannot cross membranes – so may be apparent at birth or soon after: coarse facial features, joint contractures, heart valve disease, cataracts, loss of or failure to achieve milestones. Rarely present to ED.
[kb] When to suspect an undiagnosed metabolic disorder:
Neurologic signs, hypotonia, esp decreased conscious state more severe than expected from degree of shock/hypoglycaemia
Abnormal odours – uncommon
FHx: unexplained death / SIDS in siblings, Consanguinity (usually Autosomal Recessive conditions) – but most children with IEM have a non-contributory family history
[RR] Differential diagnoses:
sepsis (decreased temp, tachycardia, tachypnea)
– can co-exist or precipitate IEM crisis (esp for galactosaemia)
pneumonia / other respiratory condition, hypoxia
NAI / shaken baby
congenital cardiac disease
electrolyte disturbances, CAH
[kb] What tests to request (during the episode of physiologic stress) – contents of our local ready-made bag (tube colours)
Claudius et al suggest: U&E, Cr, glucose, VBG, FBC, ammonia & lactate (both need special handling), urine dipstick for ketones & specific gravity
(consider: LFTs, INR, CK for myopathy)
Urine & blood cultures as sepsis is major differential
[RR] High Anion Gap (causes=shock, DKA, renal failure, poisoning, metabolic disease)
[AM] Where to draw the line for screening tests? How useful are specific clinical clues? (ie, just do a whole battery of tests, vs an intelligent/deductive approach)
>> hyperammonaemia can occur with other causes of acidosis due to down-regulation of the urea cycle
>> “inappropriate” large ketosis with fasting <12 hrs suggestive of organic acidaemia, but there are exceptions (complicated)
>> hypoglycaemia without ketones suggests Fatty Acid Oxidation disorder, BUT
>> normoglycaemia is more common in IEM (so don’t discount possibility of IEM if glucose normal)
[kb/AM] ED management of suspected IEM crisis (new diagnosis):
nil by mouth: stop the damaging substrate
call an expert
[cp] (individual conditions to be discussed in brief next time)
[all] Goodbye, thanks for listening
Claudius I, Fluharty C, Boles R.
The emergency department approach to newborn and childhood metabolic crisis.
Emerg Med Clin North Am. 2005 Aug;23(3):843-83, x. Review. PubMed PMID: 15982549.