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`
`Archives ofDiieaie in Cliiki'hmxl 1992; GT: BIN—1391
`
`I38?r
`
`PERSONAL PRACTICE
`
`
`
`Intercurrent illness in inborn errors of intermediary
`metabolism
`
`Marjorie A Dixon, I V Leonard
`
`Abstract
`in
`Metabolic decompensation may occur
`patients with disorders of intermediary meta-
`bolism during intercurrent illness. To prevent
`complications it is normal practice to change
`the diet
`to an ‘emergency regimen‘. The
`mainstay ofthis is a high carbohydrate intake,
`using soluble glucose polymer, given as
`frequentdrinksbydayandduringthenight.
`Additional therapyis given for some disorders.
`Practical details of the treatment are outlined.
`
`(Ami Dis Child IWZfiTrlRT-fl)
`
`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 ‘cincrgcncy regimen. The
`poi-pone of this paper is to outline the principles
`and practice of these regimens.
`
`Principles
`During illness and fasting various metabolic
`adaptations occur.2
`
`(A) PROTEIN rn‘rnnotlsst
`There is constant turnover of tissue protein and
`overall,
`the rate of protein synthesis exceeds
`that of breakdown so 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 carabolism.
`The nitrogen moiety of amino acids 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) suusrmrcs FOR ENERGY PRODUL'I'ION
`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 necessary 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 tissue stores. Free fatty acids can be
`utilised by many tissues, such as the heart and
`skeletal muscle, but they cannot enter the 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 catabolisrn
`and glycerol from lipolysis are substrates for
`gluconeogenesis.
`The purpose of the emergency regimen is 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 regimen is essentially
`similar for all disorders. A solution of glucose
`polymer is 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 more likely 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 preparations of 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-
`hyclration solution supplemented with glucose
`
`Horizon Exhibit 2003
`
`Horizon Exhibit 2003
`Par v. Horizon
`IPR2017-01767
`
`Par V. Horizon
`
`IPR2017—01767
`
`The Hospital for
`Sick Children and
`The Institute of
`Chiid Health,
`London
`Marjorie A Dixon
`J V Leonard
`Lhrrespimlence lo:
`Professor] v Leonard,
`Medical Unit.
`lnalitute of Child Health,
`30 Guilford Sireel.
`[notion WCIN lEH.
`
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`
`Emergency regimu
`Age
`Glucose pobnmr
`(wars)
`(humiliation
`% $chth in!“
`
`Deity mime
`
`Frequency
`
`I 511—200 mlIkg
`40
`[0
`[LI
`Initially every
`95 mll‘k
`60
`IS
`l—Z
`two hours
`IND—l
`ml
`Ill}
`20
`2—6
`nlght and rlay
`lilll—llilltlml
`RD
`20
`o—ltl
`
`
`
`25 I00>10 2000 ml
`
`3] kcal=4- Is to.
`
`polymer to the required concentration. (Practice
`note: oral tehydralion 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 sohilions using an
`appropriate sized scoop which is quick and
`easy. These solutions can also be frozen and
`thawed when needed at home or in hospital. All
`proprietary liquid glucose polymer solutions
`have a concentration of 50% carbohydrate or
`more, for example, Fortical (Cow and Gate) and
`Liquid Maxijtll (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 may still
`be possible to feed orally by giving the drinks as
`frequent sips (for example 10 ml 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 periphcral 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 overcome this it is our
`practice to teach a three stage approach.
`(1) If the parents are uncertain whether their
`child is unwell
`(or
`inst
`tired) because they
`appear lethargic, initable, 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 children it 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
`
`Dimemard
`
`regimen of drinks every two hours should be
`started. There is some flexibility 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
`improve the usual diet is 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 importance is the ability to recognise
`encephalopathy with the child becoming less
`responsive, often with a glazed look.
`Parents may face difi'tculties if the child does
`not take all the recommended volumes of feed.
`The quantities necessary vary both with the
`underlying inborn error and the intercurrcnt
`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).
`Most patients 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 rte-established.
`ln infants,
`additional glucose polymer
`is added to the
`formula food. 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.
`Whenever the child has been ill it is usual for
`us to discuss the emergency regimen carefully,
`checking that the parents knew what to 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 minimal stress;
`therefore the need for careful management of all
`mtercurrent illness.
`
`Specific treatment
`This basic emergency regimen is suitable for
`disorders of carbohydrate metabolism including
`glycogen storage diseases, fructose-l, 6-diphos-
`phatase deficiency, and ‘ketotic hypoglycaemia‘.
`However,
`in other metabolic disorders the
`emergency regimen is combined with specific
`treatment.
`
`MAPLE SYRUP URINE otsmsn (MSUD)
`In MSUD the branched chain ketoacid de-
`hydrogenase is defective. This enzyme is the
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`Imam-rent illness in inborn mm of mimediory metabolism
`
`I389
`
`second step on the catabolic pathway of the
`three branch chain amino acids (BUM): leucine,
`isoleucine, and 1::ljne.This pathway is the
`major route ford
`sal of the BCAA. As it is
`blocked in MSUls
`the BCAA and respective
`kctoacids 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 obiective of
`treatment during illness is to increase the rate of
`protein synthesis by giving a high energy intake
`as glucose with or without fat. Although the rate
`of protein synthesis may increase initially the
`concentration of the essential amino acids other
`than the BCM will soon become rate limiting.
`To prevent this supplements of the BCAA free
`
`
`
`Phenvlbutyrate
`#
`Phenylacetata
`
`HEPATIC NITROGEN
`POOL
`Alanine
`Asparrate
`Glutamina
`Glutamate
`
`Glycine
`and
`Benzoatn
`
`other compounds
`Phanylacatyl glutamine
`
`
`AMMONIA
`”WWW“?
`
`16>
`
`CAHBAMYLPHOSPHATE
`
`ORNITHINE
`
`CITRU LLINE
`
`
`
`
`
`AHGINOSUCCINATE G)
`
`UREA
`
`®
`
`AHGININE
`
`Fumarata
`
`URINE
`
`Hepatic nitrogen mtobolism Uno on majorproduct ofniirogen rotations-m. is synthesised
`within the urea miefiom
`riots and ammonia. Defect: ofeach step in the cycle have been
`identified. { l i Cdrhamipimsphute muhetute deficiency. [2) Umirhrlm: curharnjviiranifemw
`deficit!
`._(3) Argimsumnate Wham“ dc cunt)! (cinuilimmia) (4)11 mastication
`buss d9 may (argimru‘t‘inic acidtm‘a) ( )i‘lrgmare deficiency In there
`isorders sadism
`banknote and sodium phoryl'ocmte (orphemllbmymte) are used to reduce theflwr m the arm:
`cycle Remitll' mnjngared upon the gfim'ne inform hippamte and phmi'nremre conjugated
`with ghmmeiofmn pkmiacegrl gimornnw. Both ofthese compounds are rapidlv excreted
`in the mine reducing the accumulation of ammonia and ammo acids.
`
`amino acids should be given.5 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
`[he child is vomiting. 5 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 who have been unable to
`tolerate bolus feeds. Parenteral nutrition, using
`a BCAA free amino acid 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 pmolii
`some Ieucine 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 lcucine between 200—700 umolfl. 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 fliese amino acids then
`becomes necessary, in doses of 50—300 mgiday.
`To do this a solution of the amino acids is made
`{providing 100 mg of amino acid in [0 ml) and
`the required amount added to the feed. We do
`not routinely give valine and isolcucine supplew
`ments’ as not all patients need them and this
`practice could cause imbalance in amino acid
`concentrations. Hypoltalaemia may develop
`during the recovery phase.
`
`PHENYLxeroNURm (PRU)
`Many centres do not give patients with PKU an
`emergency regimen or monitor plasma pheny-
`[alanine 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 promote nitrogen excretion
`via alternative pathways. Sodium benzoate is
`most widely used. It is conjugated with glycine
`to form hippurate,
`l mole of nitrogen being
`excreted for reach 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
`benzoare because it is conjugated with glutamine
`to form phenylacetylglulamine, 2 moles of
`nitrogen being excreted for each mole of
`phenylbutyrate given.
`During illness protein breakdown may cause
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`Dixon, Leonard
`
`is to reduce the
`the aim of treatment
`but
`accumulation of propionate by diminishing
`production and increasing disposal.
`In addition to thestandard emergency regimen
`to reduce protein breakdown and amino acid
`catabolism, propinnate production from the gut
`is
`reduced by giving metronidazole (or an
`alternative antibiotic). The removal of propionyl
`groups is enhanced by giving L-carnitine. This
`forms propionyl carnitinc which is excreted in
`the urine. Carnitine is given either orally or
`intravenously in a dose of
`[00 mgfkgfday.
`Higher dimes have been used although their
`value and complications have not been assessed
`critically. In methylmalonic acidaemia there is
`usually massive excretion of methylrnalonate
`in the urine with obligatory simultaneous losses
`of sodium and potassium. These patients also
`have a concentrating and acidification defect in
`the kidneys so it is essential to give sufficient
`fluid with supplements of sodium bicarbonate
`(2—3 mnlolfkg)
`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 iudgment 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) Ismieric acidaemic
`lsovaleric 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 mgf
`kglday) and glycine (250 mgikgfday). These are
`coniugated to form isovalerylcarnitine and iso-
`valerylglycine respectively, both being rapidly
`excreted in the urine. This treatment can be
`given orally or intravenously.
`
`(for example,
`(c) Other organic octdaemias
`3-methylrmtonylgbtcinurio, glutaric nddnr'in me
`
`D I
`
`n 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 0F FATTY MSID OXIDnTIDN
`
`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 Lcamitine is widely used
`but is somewhat controversial;
`there is little
`detailed critical work. Carnitine is essential in
`
`1390
`
`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 phenylbulyrate are
`given in a dose of 250 mg/kglday but can be
`temporarily increased to 500 mgfkg/day during
`illness.
`Another consequence of these disorders is
`that arginine becomes an essential amino acid
`(except in arg'inaae deficiency). During ill-us
`the normal arg'inine supplements, 100 mgl'kg!
`day, should be given.
`In citrullinaemia and
`argiuinosuccinic aciduria, argininc should be
`given in larger doses of up to 700 mgfkgfday 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 phenylaoetate, and
`arginine should be given intravenously.
`Patients should be monitored with regular
`measurement of plasma ammonia and quantita-
`tive plasma amino acids. Protein can be reintro-
`duced once the ammonia is less than 80 untold.
`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 deficiency of
`fumarylaoetmoetase,
`the last enzyme of
`the
`oatabolic pathway of tyrosine, with resultant
`accumulation of succinylacetone and related
`metabolites. Patients are usually treated with a
`diet restricted in tyrosine and phenylalanine.
`Although it is not common to use an emergency
`regimen in this disorder, deoompcnsation 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 metlgllmlonic actdmia
`Propionic and methylmalonic acidaemia are
`caused by inherited enzyme defects in the
`pathways of propionate catabnlism. Propionate
`is formed from several sources including the
`amino acids isoieucine, valine, methionine, and
`threonine, by anaerobic bacteria]
`fermenta—
`tion in the gut and catabolism of odd chain fatty
`acids. Although amino acids are widely regarded
`as the maior source of propionate, only about
`50% of propionate is derived fmm breakdown
`of amino acids.“ About 20% is derived from the
`gut“ and the rest
`(30%) probably from the
`catabolism of odd chain fatty acids.7 The toxic
`metabolites and the mechanisms responsible for
`all the clinical problems are not well understood
`
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`{murmur illness in labor-II arm offiuemrdiary metabolism
`
`139]
`
`primary systemic carnitine deficiency and may
`be helpful
`in reversing decompensatiou 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 monitor patients
`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 may initially be
`necessary, but it may add no the burden of care.
`The correct balance needs to be found between
`overzealous intervention and the risk of compli-
`cations. Furthermore, rhe needs of each child
`and their family must be iudgod carefully and
`
`the instructions adjusted to their own individual
`requirements.
`
`ton and D]: Margaret
`We would like to thank Dr Filer Chi
`Lawson for their constructive criticism 0 Ill: manuscript.
`
`Nore: References about the inlrnm errors have, in general. only
`er til.
`hoefllgiven when: ll: statermnl is not mandated In Scriver
`
`I ScriverCR, Beaudet M ., Sly WS, Valle D, eds, Tire aerobatic
`basis ofinltzr'itetf disease. 6th Ed. New York: McGraw—Hill,
`I989.
`Bilathnrl'nugr
`2 Newsholme EA, Leoeh AR.
`for the medical
`,I_983.
`rem. (lichester: john W"
`3 Rennie M], Edwards RHT,
`y D, MatthewsDE],
`measured by stable isotope techniques:
`the e
`Wolrnau SL, Milward D] Muscle protein aw
`feeding and lining. ClmSer' I982;63:S Ill—2!.
`4 Thorn
`GN, Br—II IL, Waller 1H, rt rd. Pro-loin and
`leuerne metabolism in
`syrup urine disease. Am 1
`PW 99095455440.
`5 Thompson GN, Francis DEM, Halliday D. Acute illness in
`maple syrup winediaease: dynamics ofprutein metabolism
`
`l99l;ll9:
`£54le for malignant. _7 Pediatr
`1:
`innate
`a in to
`errors
`Er Tia-Impaon GN. Walter IH. an ll er 24:: Sources of
`meolism. Mmbolr'snr 1990;an: "33—7.
`PM
`3’ Sirai D. Prudlrom C. Thompson GN, Marioui A, Sauduhray
`1M, Bronson IL Possible contributions of odd chain fatty
`acid oxidation to propiunate productionIn methyimalmlic
`and
`ionic acidaerrlia. Pediatrfles 1992; 31: IRA.
`B D'Angro ,Leornrd JV, Dilull M]. Rural tubular function
`izrrsg—néthflmahnie actdaem'ia. Ear j Padrarr'
`IWIuSfl:
`
`Appendix Mmfarflrred prnd'rrrtr used in ample syrup urine disease (MSUD) and ma cycle dimrdau 1‘ HUD)
`Product
`Vitamins and minerals
`Cements
`Amimacidr
`Energy
`Cardohydrw
`For
`{WW 5) {gflfllgj (anIMg‘J and! g]
`
`
`
`Ml Maplew Irina disease: him
`products come! all marine acids exoepr lire branched chain arm, lent-tire, More, will with:
`4'62
`54
`23
`Infant formula
`Ful range
`Analog MSUD (1]
`15'5
`Mammals] MSUD (l)
`30
`300
`51
`{0‘5
`Full range
`Suitable from 2 gears of age,
`solubility
`Minimum MSUD (I)
`‘7
`290
`34
`{0'5
`Full range
`Suitable from ll years of age.
`good solubility
`MSUD Md (l)
`“I
`320
`Nil
`Nil
`Limited range
`low solubility [not suitable
`for conIinutma Feeds)
`MSUD l
`(2}
`49
`290
`29 (sucrose)
`Nil
`Fa! range
`For infants:
`lriglt sucrose moment,
`requires far to be added
`MSUD 2 (2)
`65
`ill]
`22 [sucrose]
`Nil
`FII range
`For children
`MSUDdiel powderfil)
`I2
`433
`63
`20
`Full range
`Infant formula
`{Biflmryelediswden MWWnauixmeofemwlandmn—ewiofmnoandr
`Dialamine (I)
`3-60
`62 (54 3 sucrose]
`Limited range, low conlent
`Nil
`Orange flavoured, high sucrose contcnl
`UCD l (2)
`as
`For iru'anls: requires carbohydrate and
`260
`8 I) (sucrose)
`Nil
`Full range
`fat
`to be added
`
`290 For children 6'!) (sucrose) Nil Full range
`SI
`UCD Z {2)
`
`
`
`,Middleoex: {3) Mead johnson Nutritionallr, l-Iounsltwr, Middlesex. [n the UK:
`rIerlirie SubsIanoes and can be prescribed on an FPIO
`
`On]
`the SHS
`Manufacturer: (1) Scientific Hospital Supplies (th),LIve1-pool (2) Milupa,H
`oducts have been approved bthe wwtmdh
`']
`=4 18 k
`
`Page 5 0f 6
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`

`

`Dmnloaded from adcbmjcom ctr: October 1?, 2014 — Published by groupbmjcom
`
`ADC
`
`lntercurrent illness in inborn errors of
`intermediary metabolism.
`M A Dixon and J V Leonard
`
`Arch Dis Chiid 1992 67: 1387-1391
`doi: 10.1136!adc.6?.11.1387
`
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