Author: Edward Snelson / Codes: / Published: 18/05/2016
Inborn errors of metabolism (IEMs) are disorders of chemical pathways. These diseases led to dangerous deficiencies or excesses of chemicals. While each individual IEM is rare, together they form a significant burden of disease to children. When it comes to metabolic problems in small children, it is easy to assume that this is a specialist area. It may be scary but it is so simple that I guarantee that nothing in this post is complicated or difficult to remember. In fact there are really only three things to know about children’s inborn errors of metabolism. That’s right, just three. Let’s start with the hardest one in practice:
Think about the possibility of a metabolic problem
When a baby (In this context, that’s any child that stays within 1 metre of where you left them for five minutes) presents with vague symptoms, the emergency physician should consider five broad categories of causes to the problem.
Fig. 1 – The ‘big five’ causes of a baby being non-specifically unwell.
If this were a Wilder Penfield diagram, the thumb would be bigger than the rest of the hand put together. Of course infection is always the most likely but the others need to be considered. In all five groups, the likelihood is that the child will present with vague symptoms such as being less interested in feeds, being miserable and doing non-specific things like vomiting. Children with metabolic disorders can also present just like this.
The best way to avoid missing a metabolic problem is to look for any clue of any of the ‘big five’ listed above. If there is no clear explanation for the child being “off”, don’t just think metabolic. The other causes (don’t forget that injury includes NAI) are just as important and need to be actively considered.
Do extra tests
A capillary or venous blood sugar level is a routine (and I do not use that word lightly) test in any baby who is ‘just not quite right’ but for non-specific presentations there are a few more that will increase the likelihood of detecting a metabolic problem early. The simplest of these is a blood gas. Septic and otherwise ill babies have moderately raised lactates. In some metabolic disorders the lactate is disproportionately high and may be in double figures. Similarly unexpectedly high or low pH results should prompt further consideration of a metabolic problem. If your gas machine gives electrolyte results, look at these. They may be really abnormal if this is a metabolic problem. For example, congenital adrenal hyperplasia can present with hyponatremia, hyperkalaemia and shock. If you are getting a good free flowing sample when you place a cannula, first obtain your usual ‘sick baby tests’ (Culture, FBC, U&E, Ca, LFT, CRP etc) and then fill one more of each bottle (plain, fluoride and heparin) with blood. Your department may have specific bottles that they want in these circumstances so check before you stop taking your sample. One sample that needs special treatment is the extra Lithium Heparin sample. This needs to be cooled by having an adjacent bag of ice and it needs to be tested by the lab within an hour if you are to get a useful ammonia result.
Save a life
Early diagnosis and intervention are very important in the long-term outcomes for children with inborn errors of metabolism. How do you do that when you don’t know what the problem is? When a baby presents with vomiting, a lactate of 12, a sodium of 124, a pH of 7.67, dysmorphic features and purple urine, do you know what the diagnosis is? No? Neither do I and I just made the whole thing up. One of the fallacies about metabolic problems in babies is that you have to have learned and understood metabolic medicine. You don’t need to know what the problem is to make a big difference. The diagnosis can wait. There are just three things that are going to help in the first stages. First, stop the feeds. Most metabolic pathways that go wrong are trying to process complex carbohydrates, fats and proteins. Confiscate these immediately if you want to make sure the condition does not worsen. Second, give fluid and dextrose. Whatever the toxin, dilution is usually a good thing and the chances are that the baby is fluid depleted. If indicated by the clinical situation (poor urine output, tachycardic, etc.) give a fluid bolus. As well as any fluid resuscitation with isotonic fluid, maintenance fluid with 10% dextrose should be given. This generous carbohydrate supply will shut the majority of the metabolic pathways down (fig. 3). The sodium and potassium concentration of the maintenance fluids will depend on other factors and serum levels will need to be monitored closely. If necessary ask your ICU or neonatal unit to provide help providing special combinations such as 10% dextrose with 0.9% NaCl if needed.
Fig 3. Metabolic pathways look complicated. This excellent diagram from The Children’s Mitochondrial Disease Network is one of the most simple summaries available and it is still daunting to any mortal physician. The simple explanation is that when metabolic pathways go wrong, you end up with too much of some things and too little of others. Thirdly, give vitamins. I know that this sounds like an accidental turn into alternative medicine but there are some metabolic conditions that are amenable to treatment with large quantities of certain vitamins. What to give? Well, either your department has an emergency metabolic box for exactly this circumstance or you don’t in which case the paediatric metabolic consultant you are phoning can advise. You have phoned the paediatric metabolic consultant at this point haven’t you? Of course you can delegate this job to the paediatric medic on call. When someone does speak to the paediatric metabolic consultant, ask them what the diagnosis is. I am willing to bet that they won’t know either. Instead they will want to talk about what you can do while they do expensive tests in order to make a diagnosis. They will likely suggest three things…
Acknowledgements – Thanks to Dr Judith Gilchrist (paediatrician and Paeds EM consultant) and Dr Chris Connolly (Consultant Emergency Medicine) for their help in writing this.