`
`Archives ofDisease in Childhood 1992; 67; 1387-1391
`
`1387
`
`PERSONAL PRACTICE
`
`
`
`Intercurrentillness in inborn errors of intermediary
`metabolism
`
`Marjorie A Dixon, J V Leonard
`
`Abstract
`in
`Metabolic decompensation may occur
`patients with disorders of intermediary meta-
`bolism during intercurrentillness. To prevent
`complications it is normal practice to change
`the diet
`to an ‘emergency regimen’. The
`mainstay of this is a high carbohydrate intake,
`using soluble glucose polymer, given as
`frequent drinks by day and during the night.
`Additional therapy is given for some disorders.
`Practical details of the treatment are outlined.
`
`(Arch Dis Child 1992;67:1387-91)
`
`is the mainstay of treatment for many
`Diet
`inborn errors of intermediary metabolism,!
`Patients are stabilised on a diet appropriate for
`their disorder
`that will provide them with
`sufficient nutrients and energy to grow and
`develop normally. However metabolic stress
`such as intercurrent infections may precipitate
`decompensation and cause complications. To
`prevent these it is common for the diet to be
`changed to an ‘emergency regimen’. The
`purpose of this paper is to outline the principles
`and practice of these regimens.
`
`Principles
`During illness and fasting various metabolic
`adaptations occur.”
`
`(A) PROTEIN CATABOLISM
`There is constant turnoverof tissue protein and
`overall,
`the rate of protein synthesis exceeds
`that of breakdownso there is net gain and hence
`growth.? However, during illness the rate of
`protein breakdown normally exceeds that of
`synthesis with net production of amino acids
`and an increase in their irreversible catabolism.
`The nitrogen moiety of aminoacids is converted
`to ammonia and then to urea. The carbon
`skeleton of amino acids is progressively cata-
`bolised to form fuels for energy production
`including acetyl CoA, pyruvate, and inter-
`mediates of the Krebs cycle.
`
`(B) SUBSTRATES FOR ENERGY PRODUCTION
`Glucose is a major fuel for energy metabolism
`but glycogen reserves for glucose production
`during fasting are relatively limited in children.
`To maintain a supply of substrate for energy
`production and protect glucose supply to the
`
`is mecessary to mobilise alternative
`brain it
`fuels, including free fatty acids, ketones, and
`gluconeogenic precursors.
`On fasting, as glucose concentrations slowly
`fall, there is a decrease in the insulin:glucagon
`ratio with mobilisation of fatty acids from
`adipose Ussue stores. Free fatty acids can be
`utilised by many tissues, such as the heart and
`skeletal muscle, but they cannotenterthe brain.
`In the liver,
`free fatty acids are partially
`oxidised to ketones which are water soluble and
`can enter the central nervous system. Alanine
`and other amino acids from muscle catabolism
`and glycerol from lipolysis are substrates for
`gluconeogenesis.
`The purpose of the emergency regimenis to
`prevent
`the changes that occur with fasting.
`The aim is to reduce protein catabolism and
`hence the accumulation of potentially toxic
`metabolites. By giving an adequate supply of
`glucose the mobilisation of alternative fuels is
`also reduced.
`
`Practical aspects of emergency regimens
`The core of the emergency regimenis essentially
`similar for all disorders. A solution of glucose
`polymeris given as the major source of energy
`because it is simple, palatable, and usually well
`tolerated. Fat emulsions can provide additional
`energy, but these are less well
`tolerated; fat
`delays gastric emptying and is morelikely to
`cause vomiting so we do not use them routinely.
`It
`is also contraindicated in some disorders,
`such as inborn errors of fatty acid oxidation. In
`most instances we would start by giving feeds
`orally. There are important advantages to oral
`feeding. It can be started at home; more glucose
`can be given than by peripheral
`intravenous
`infusions and medicines can be given. This can
`be important as intravenous preparationsof the
`medicine are often not readily available. If oral
`feeding is not possible, nasogastric feeding,
`either bolus or continuous, should be tried
`before intravenous therapy for the same reasons.
`The concentrations and volumes of solution
`given will depend on the age of the child.
`Relatively higher volumes and lower concentra-
`tions are used in infants compared with older
`children (table).
`Insufficient fluid combined
`with high concentrations of glucose polymer
`that can cause diarrhoea may exacerbate the
`effects of illness. If the child is likely to become
`dehydrated it is advisable to give an oral re-
`hydration solution supplemented with glucose
`
`LUPIN EX. 1009
`
`1 of 6
`
`The Hospital for
`Sick Children and
`The Institute of
`
`Correspondence to:
`Professor J V Leonard,
`Medical Unit,
`Institute of Child Health,
`30 Guilford Street,
`London WCIN 1EH.
`
`1 of 6
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`
`
`Emergency regimen
`Age
`Glucose polymer
`(vears)
`concentration
`% keali 100 ml*
`
`Daily volume
`
`Frequency
`
`150-200 ml/kg
`40
`lo
`ol
`Initially every
`95 milk,
`60
`I
`1-2
`two hours
`1200-1500
`ml!
`«80
`200
`26
`night and day
`1500-2014) ml
`80
`20
`610
`
`
`
`625) 100>10 2000 ml
`
`*] keal=4-18 kj.
`
`polymerto the required concentration. (Practice
`note: oral rehydration solutions do not contain
`sufficient glucose on their own.) The solution is
`given orally as small frequent drinks or enterally
`via a nasogastric tube, normally at intervals of
`two hours night and day. This is usually well
`tolerated. It is particularly important not
`to
`allow the child to go for long periods (>4 hours)
`between drinks during the night.
`Parents are taught to make solutions using an
`appropriate sized scoop which is quick and
`easy. These solutions can also be frozen and
`thawed when needed at homeorin hospital. All
`proprietary liquid glucose polymer solutions
`have a concentration of 50% carbohydrate or
`more, for example, Fortical (Cow and Gate) and
`Liquid Maxijul (Scientific Hospital Supplies),
`and are not suitable for an emergency regimen
`unless diluted to an appropriate concentration.
`In our experience these are less palatable and
`more likely to induce vomiting or diarrhoea if
`given undiluted.
`In some children the first symptom of any
`illness is refusal to eat or drink. If so, we often
`teach the parents how to use a nasogastric tube
`at home,
`thereby reducing the need for a
`hospital admission.
`If the child has occasional vomits, it maystill
`be possible to feed orally by giving the drinks as
`frequent sips (for example 10 mi every 10
`minutes) or as a continuous nasogastric feed
`either at home or in hospital. However, if the
`child is vomiting frequently or is obviously
`unwell
`then intravenous therapy is essential.
`Concentrated glucose solutions should be used:
`10% dextrose by peripheral drip or more
`concentrated through a central
`line. Hyper-
`glycaemia may develop so blood glucose con-
`centrations should be monitored regularly.
`
`Instructions for parents
`Many parents have difficulty in knowing both
`when to start
`the emergency regimen and
`exactly what to do. To overcomethis it is our
`practice to teach a three stage approach.
`(1) If the parents are uncertain whether their
`child is unwell
`(or
`just
`tired) because they
`appear lethargic, irritable, or off colour then
`an emergency regimen drink should be given.
`Next, a conscious decision is made to reassess
`the child within one to four hours, depending
`on the age and disorder. In some childrenit is
`possible to monitor the disorder by using simple
`tests at home. These are discussed later under
`the individual disorders.
`(2A) If on review the child has improved, the
`normal diet is resumed. (B) If on reassessment
`there is no improvement
`the full emergency
`
`Dixon, Leonard
`
`regimen of drinks every two hours should be
`started. There is someflexibility in the frequency
`of the drinks particularly in the older children
`and during recovery. During illness most
`children will automatically stop eating the
`normal diet, and once the child starts to
`improvethe usual dietis gradually reintroduced.
`(3) If the child is refusing to take the drinks, is
`vomiting frequently, or becoming encephalo-
`pathic then they should be admitted to hospital
`for assessment. The parents need to be aware of
`and recognise clinical signs of deterioration. Of
`particular importanceis the ability to recognise
`encephalopathy with the child becoming less
`responsive, often with a glazed look.
`Parents may face difficulties if the child does
`not take all the recommended volumes of feed.
`The quantities necessary vary both with the
`underlying inborn error and the intercurrent
`illness. It is particularly important that patients
`with maple syrup urine disease and methyl-
`malonic acidaemia should have close to the
`recommended volumes (see below). By contrast
`those with glycogen storage disease may be
`controlled satisfactorily with smaller volumes.
`Patients with gastroenteritis will in general need
`more fluid than those with upper respiratory
`tract infections.
`It should be emphasised that the basic emer-
`gency regimen must not be continued for long
`periods of time because it does not provide
`adequate nutrition and will cause nutritional
`deficiencies. Early clinical signs of such defi-
`ciencies include skin rashes (particularly at the
`site of adhesive tape for nasogastric tubes).
`Mostpatients can be gradually returned to their
`usual diet within a few days.
`When the diet is being reintroduced addi-
`tional high carbohydrate drinks are given until
`the normal diet is re-established.
`In infants,
`additional glucose polymer
`is added to the
`formula feed. For patients on low protein diets
`the protein intake is usually increased daily,
`giving one quarter, one half, three quarters of the
`usual
`intake,
`resuming the normal protein
`allowance by day four.
`Wheneverthe child has beenill it is usual for
`us to discuss the emergency regimen carefully,
`checking that the parents knew whatto do and
`that the emergency regimen meets the needs of
`their child. It is important to recognise that the
`course of these disorders is often unpredictable.
`The children may have a serious infection
`without any problems, but then develop severe
`decompensation after apparently minimalstress;
`therefore the need for careful managementofall
`intercurrentillness.
`
`Specific treatment
`This basic emergency regimen is suitable for
`disorders of carbohydrate metabolism including
`glycogen storage diseases, fructose-1, 6-diphos-
`phatase deficiency, and ‘ketotic hypoglycaemia’.
`However,
`in other metabolic disorders the
`emergency regimen is combined with specific
`treatment.
`
`MAPLE SYRUP URINE DISEASE (MSUD)
`In MSUD the branched chain ketoacid de-
`hydrogenase is defective. This enzyme is the
`
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`Jntercurrent illness in inborn errors of intermediary metabolism
`
`1389
`
`second step on the catabolic pathway of the
`three branch chain amino acids (BCAA): leucine,
`isoleucine, and ana This pathway is the
`major route for disposal of the BCAA. Asit is
`blocked in MsUD the BCAA and respective
`ketoacids accumulate and are responsible for
`the encephalopathy. Losses of BCAA and
`ketoacids in the urine and through other
`pathways are low* so the only way to reduce
`plasma concentrations is for the BCAA to be
`incorporated into protein. The abjective of
`treatmentduring illness is to increase the rate of
`protein synthesis by giving a high energy intake
`as glucose with or withoutfat. Although the rate
`of protein synthesis may increase initially the
`concentration of the essential amino acids other
`than the BCAA will soon becomerate limiting.
`To prevent this supplements of the BCAA free
`
`amino acids should be given.* Our aim is to
`provide the full energy requirement and the
`child’s usual quantity of BCAA free supplement.
`This is not always possible orally, particularly if
`the child is vomiting. A useful alternative is
`continuous nasogastric feeding of Maxamaid
`MSUD (Scientific Hospital Supplies,
`see
`appendix) supplemented with extra glucose
`polymer. We have successfully used this to treat
`patients with MSUD whohave been unable to
`tolerate bolus feeds. Parenteral nutrition, using
`a BCAAfree aminoacid solution, is an alterna-
`tive if enteral feeding fails but this is available
`in few centres. Regular daily quantitative
`measurements of the BCAA are essential
`to
`monitor progress and to determine when pro-
`tein can be reintroduced.
`Once the plasma leucine concentration falls
`below 800 pmol/l
`some leucine usually as
`natural protein can be reintroduced, and is
`increased to the usual intake according to the
`plasma concentrations. Our aim is to keep
`plasma leucine between 200-700 pmol/l. During
`the recovery phase concentrations of the iso-
`leucine and valine may fall to low concentrations
`and become rate limiting for protein synthesis.
`Supplementation of these amino acids then
`becomes necessary, in doses of 50-300 mg/day.
`To dothis a solution of the amino acids is made
`(providing 100 mg of amino acid in 10 ml) and
`the required amount added to the feed. We do
`not routinely give valine and isoleucine supple-
`ments? as not all patients need them and this
`practice could cause imbalance in amino acid
`concentrations. Hypokalaemia may develop
`during the recovery phase.
`
`PHENYLKETONURIA (PKU)
`Manycentres do not give patients with PKU an
`emergency regimen or monitor plasma pheny-
`lalanine concentrations during illness. However
`with increasing emphasis on improving meta-
`bolic control, an emergency regimen is likely to
`be necessary. It should be similar to that used in
`MSUD.
`
`UREA CYCLE DISORDERS
`The urea cycle converts waste nitrogen into
`urea, via a series of enzymes (figure). Inborn
`errors have been identified for each step and
`may cause accumulation of ammonia and gluta-
`mine which are neurotoxic and may cause a
`severe encephalopathy.
`Patients are treated with a low protein diet
`and medicines which promotenitrogen excretion
`via alternative pathways. Sodium benzoate is
`most widely used. It is conjugated with glycine
`to form hippurate,
`1 mole of nitrogen being
`excreted for each mole of sodium benzoate
`given. Phenylbutyric acid can also be given
`either as the free acid or the sodium salt but is
`less palatable. Phenylbutyrate is metabolised in
`vivo to phenylacetate, and is more effective than
`benzoate because it is conjugated with glutamine
`to form phenylacetylglutamine, 2 moles of
`nitrogen being excreted for each mole of
`phenylbutyrate given.
`During illness protein breakdown may cause
`
`3 of 6
`
`Phenylbutyrate
`HEPATIC NITROGEN
`POOL
`Alanine
`
`Aspartate
`Glutamine
`
`Glutamate
`Glycine
`
`and
`Benzoate
`other compounds
`
`Phenylacety! glutamine
`
`Phenylacetate
`
`AMMONIA
`
`Fippuraig
`
`|
`
`CARBAMYLPHOSPHATE
`
`ORNITHINE
`
`CITRULLINE
`
`
`
`
`UREA
`
`ARGININE
`
`
`ARGINOSUCCINATE ()
`
`Fumarate
`
`URINE
`Hepatic nitrogen setabolisr: Urea, the majorproduct ofnitrogen catabolism,is synthesised
`within the urea cyciefrom aspartate and ammonia. Defecis ofeach step in the‘cycle have been
`identified. (1) Carbamylphosphate synthetase deficiency. (2) Ornithine carbamyltransferase
`deficiency. (3) Arginosuccinate synthetase deficiency (citrullinaemia). (4) Arginosuccinate
`lyase deficiency (arginosuccinic aciduria), (5) Arginase deficiency. [m these
`disorders sodium
`benzoate and sodium phenylacetate (or phenylbutyrate) are used to reduce the flux in the urea
`evele. Benzoate ts conjugated with theglycine toform re andphenylacetate conjugated
`with ghitamine to form phenylacetyl glutamine. Both of these compounds are rapidly excreted
`in the urine reducing the accumulation of ammonia and amino acids.
`
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`
`rapid accumulation of ammonia and glutamine.
`In addition to the basic emergency regimen the
`usual medication should continue to be given.
`Both sodium benzoate and phenylbutyrate are
`given in a dose of 250 mg/kg/day but can be
`temporarily increased to 500 mg/kg/day during
`illness.
`Another consequence of these disorders is
`that arginine becomes an essential amino acid
`(except in arginase deficiency). During illness
`the normal arginine supplements, 100 mg/kg/
`day, should be given.
`In citrullinaemia and
`argininosuccinic aciduria, arginine should be
`given in larger doses of up to 700 mg/kg/day to
`replenish ornithine that is not reformed as a
`result of the metabolic block. All the medication
`should be given in frequent small doses. If the
`child cannot tolerate oral fluids or medicines
`sodium benzoate, sodium phenylacetate, and
`arginine should be given intravenously.
`Patients should be monitored with regular
`measurement of plasma ammonia and quantita-
`tive plasma aminoacids. Protein can be reintro-
`duced once the ammoniais less than 80 mol/l.
`Occasionally it can be difficult to reintroduce
`protein without
`inducing hyperammonaemia
`and in these cases an essential amino acid
`supplement (for example Dialamine, Scientific
`Hospital Supplies, see appendix), can be given.
`This will promote both protein synthesis and
`the reutilisation of nitrogen to form non-
`essential amino acids thereby reducing ammonia
`accumulation.
`
`TYROSINAEMIA TYPE I (FUMARYLACETOACETASE
`DEFICIENCY)
`Tyrosinaemia type I is caused by a deficiencyof
`furnarylacetoacetase,
`the last enzyme of
`the
`catabolic pathway of tyrosine, with resultant
`accumulation of succinylacetone and related
`metabolites. Patients are usually treated with a
`diet restricted in tyrosine and phenylalanine.
`Althoughit is not common to use an emergency
`regimen in this disorder, decompensation of
`liver function and deterioration of neurological
`function can follow intercurrent infection. It is
`probably beneficial that an emergency regimen
`is given to reduce these problems. The patients
`may also need appropriate treatment for liver
`failure.
`
`ORGANIC ACIDAEMIAS
`
`(a) Propionic and methylmalonic acidaemia
`Propionic and methylmalonic acidaemia are
`caused hy inherited enzyme defects in the
`pathways of propionate catabolism. Propionate
`is formed from several sources including the
`aminoacids isoleucine, valine, methionine, and
`threonine, by anaerobic bacterial
`fermenta-
`tion in the gut and catabolism of odd chain fatty
`acids. Although aminoacids are widely regarded
`as the major source of propionate, only about
`50% of propionate is derived from breakdown
`of amino acids.° About 20%is derived from the
`gut® and the rest
`(30%) probably from the
`catabolism of odd chain fatty acids.’ The toxic
`metabolites and the mechanismsresponsible for
`all the clinical problems are not well understood
`
`Dixon, Leonard
`
`is to reduce the
`the aim of treatment
`but
`accumulation of propionate by diminishing
`production and increasing disposal.
`In addition to the standard emergency regimen
`to reduce protein breakdown and amino acid
`catabolism, propionate production from the gut
`is
`reduced by giving metronidazole (or an
`alternative antibiotic). The removal of propiony!
`groups is enhanced by giving L-carnitine. This
`forms propiony! carnitine which is excreted in
`the urine. Carnitine is given either orally or
`intravenously in a dose of 100 mg/kg/day.
`Higher doses have been used although their
`value and complications have not been assessed
`critically. In methylmalonic acidaemia there is
`usually massive excretion of methylmalonate
`in the urine with obligatory simultaneous losses
`of sodium and potassium. These patients also
`have a concentrating and acidification defect in
`the kidney® so it is essential to give sufficient
`fluid with supplements of sodium bicarbonate
`(2-3 mmol/kg)
`to replace sodium loss and
`reduce the acidosis. Patients may also need
`potassium supplements particularly during the
`recovery phase.
`It may be helpful to monitor the patient’s
`condition by measuring urine ketones but in our
`experience the parents’ clinical judgment is as
`useful for most children.
`It is important to reintroduce protein early
`(within two to three days) to prevent protein
`deficiency and additional problems such as
`rashes and vomiting.
`
`(b) Isovaleric acidaemia
`Isovaleric acidaemia is due to a deficiency of
`isovaleryl-CoA dehydrogenase, the third step in
`the pathway of leucine degradation. Isovaleric
`acid accumulates and its excretion in the urine
`can be increased by giving L-carnitine (100 mg/
`kg/day) and glycine (250 mg/kg/day). These are
`conjugated to form isovalerylcarnitine and iso-
`valerylglycine respectively, both being rapidly
`excreted in the urine. This treatment can be
`given orally or intravenously.
`
`(for example,
`acidaemias
`(c) Other organic
`3-methylerotonylglycinuria, glutaric aciduria type
`I)
`In addition to the standard emergency regimen,
`L-carnitine is widely used to increase the
`removal of acyl groups, although controlled
`studies of its efficacy are lacking.
`
`DISORDERS OF FATTY ACID OXIDATION
`
`Inborn errors at several steps in the pathway of
`fatty acid oxidation are now well described, the
`most common is medium chain acyl CoA
`dehydrogenase deficiency. To prevent illness in
`these patients the standard emergency regimen
`is used. It is important to stress early use of the
`emergency regimen to inhibit mobilisation of
`fatty acids, particularly in long chain disorders
`because decompensation may be rapid. Addi-
`tional treatment with L-carnitine is widely used
`but is somewhat controversial;
`there is little
`detailed critical work. Carnitine is essential in
`
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`Intercurrent illness in inborn errors ofintermediary metabolism
`
`1391
`
`primary systemic carnitine deficiency and may
`be helpful
`in reversing decompensation in
`disorders of medium chain fatty acids. In theory
`carnitine in long chain fatty acid oxidation
`disorders might be harmful, by promoting the
`uptake of long chain fatty acids into mito-
`chondria. Its use requires more evaluation.
`Blood glucose is often used to monitorpatients
`with these disorders, but this may give a false
`sense of security as patients may develop
`marked encephalopathy before blood glucose
`concentrations fall: treatment must be started
`before this.
`
`Conclusions
`The use of a well planned emergency regimen
`will not only help prevent episodes of metabolic
`decompensation, but will
`reduce hospital
`admissions and improve the parents’ self confi-
`dence. The policy of encouraging the family to
`bring the unwell child to hospital every time is
`intended to be supportive and mayinitially be
`necessary, but it may add to the burden ofcare.
`The correct balance needs to be found between
`overzealous intervention and the risk of compli-
`cations. Furthermore, the needs of each child
`and their family must be judged carefully and
`
`the instructions adjusted to their own individual
`requirements.
`
`We would like to thank Dr Peter Clayton and Dr Margaret
`Lawson for their constructive criticism of
`the manuscript.
`
`Note: References about the inborn errors have, in general, only
`been Biven where the statement is not substantiated in Scriver
`etal.!
`
`1 Scriver CR, Beaudet Al., Sly WS, Valle D, eds. The metabolic
`faea ere disease. 6th Ed. New York: McGraw-Hill,
`2 Newsholme EA, Leech AR. Biochemisiry for the medical
`sciences. Chichester: John Titer
`i
`y D, ieee.oe
`Wolman SL, Milward DJ. Muscle protein 5
`‘ measured by stable isotope techniques: the ona
`feeding and fasting. Clin Set 1982363:519-23.
`4 Thom
`GN, Bresson JL, Walter JH, et af. Protein and
`leucine metabolism in maple syrup urine disease, Am 7
`Physiol 1990;254:654-60.
`5 Thompson GN,Francis DEM,Halliday D. Acute illness in
`maple syrup urine disease: dynamics of protein metabolism
`and allele for mangement. 7 Pediatr 1991;119:
`354
`6 Thompson GN, Walter JH, —— JL, et a Sources of
`ionate
`n in in
`errors
`ropionate
`Ieabaliaas: Metabolism 1990;39:1133-7.
`e
`7 Sbai D, Prodhom C., Thompson GN, Mariotti A, Saudubray
`JM,Bresson JL. Possible contributions of odd chain fatey
`a oxidation to propionate production in methylmalonic
`spapeepionionic acidaemia, PediawRes 1992;31;188A,
`Leonard JV, Dillon MJ. Renal tubular function
`» igmeimal acidaemia. Fur F Pediatr 19915150:
`
`Appendix Manufactured products used in maple syrup urine disease (MSUD) and urea cycle disorders (UCD)
`Product
`Amino acids
`Energy
`Carbohydrate
`Fat
`Vitamins and minerals
`Comments
`
`(git00 g)
`(Acall100 g")
`(gi100 g)
`(gi100 g)
`
`(A) Maple syrup urine disease:
`these products contain all anima acids except the sla chain ones,
`leucine,
`Analog MSUD (1)
`15°5
`462
`54
`Full range
`Maxamaid MSUD (1)
`30
`300
`51
`205
`Full range
`
`Maxamum MSUD (1)
`MSUD Aid (1)
`MSUD |
`(2)
`MSUD 2 (2)
`MSUD diet powder (3)
`
`47
`96
`49
`65
`12
`
`20
`320
`230
`310
`433
`
`#4
`Nil
`29 (sucrose)
`22 (sucrose)
`63
`
`<05
`Nil
`Nil
`Nil
`20
`
`toleucine, and valine
`Infant formula
`maAtleNot2 years of age,
`ubility
`Suitable from § years of age.
`good solubility
`Low solubility (not suitable
`for continuous feeds)
`For infants: high sucrose content,
`requires fat to be added
`For children
`Infant formula
`
`Full range
`Limited range
`Full range
`Full range
`Full range
`
`(B) Urea cycle disorders: des pete contain a mixture of essential and non-essential amino acids
`Dialamine (1)
`360
`62 (54 g sucrose)
`Nil
`Limited range, low content
`Orange flavoured, high sucrose content
`UCD 1 (2)
`a
`For infants: requires carbohydrate and
`260
`8-0 (sucrose)
`Nil
`Full range
`fat
`to be added
`290 For children 60 (sucrose) Nil Full range
`
`UCD 2 (2)
`81
`
`
`
`, Middlesex; (3) Mead Johnson Nutritionals, Hounslow, Middlesex. In the UK:
`be prescribed on an FPO.
`ising Substances and can
`1
`
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`Downloaded from adc.bmj.com on October 17, 2014 - Published by group.bmj.com
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`ADC
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`intercurrentillness in inborn errors of
`intermediary metabolism.
`M A Dixon and J V Leonard
`
`Arch Dis Child 1992 67: 1387-1391
`doi: 10.1136/adc.67.11.1387
`
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