Diagnosis of IEM
AndEmergency Management
Susan Sklower Brooks, M.D., F.A.C.M.G.Professor of Pediatrics
Professor of Obstetrics, Gynecology and Reproductive SciencesRobert Wood Johnson Medical School
What do they have in common?
A full term 4 day old?A 2 year old from Pakistan?An 8 year old at summer camp?An 18 year old college student?
What Do They Have In Common?
1. An infectious disease?
2. A congenital heart disease?
3. An inborn error of metabolism?
4. Who cares?
An infec
tious
dise
ase?
A cong
enita
l hea
rt di...
An inbor
n erro
r of m
e...
Who cares
?
0% 0%
100%
0%
Case ReportThe 2 year old child became The 2 year old child became unresponsive while traveling with unresponsive while traveling with her parents on the New her parents on the New JerseyJersey Turnpike. Turnpike.
Summer Camp Escapade
The 8 year old went to sleep-away camp for the first time. After several days she became increasing lethargic and was brought to a local ED. On arrival she was barely arousable.
College Binge?
The 18 year old college student was brought to the ED unresponsive. She had been at a prefinal party with friends where alcohol was served.
What is the likely diagnosis?
1. Inborn Error of Metabolism?
2. Still not sure?3. Who cares?
Inborn Erro
r of M
eta...
Still not
sure?
Who cares
?
94%
0%6%
Inborn Errors of MetabolismAmino acid disordersOrganic acidemiasUrea cycle disordersCarbohydrate metabolism disordersMitochondrial disordersMitochondrial fatty acid oxidation disordersPeroxisomal disordersLysosomal storage disordersPurine and pyrimidine disordersPorphyriasMetal metabolism disorders
IntoxicationEnergy MetabolismComplex Molecules
Major Presentation Categories for Inborn Errors of Metabolism
Saudubray, JM et al, Semin Neonatol 2002: 7:3-15
Intoxication
Symptom free interval- vomiting, lethargy coma, liver failure, etcOften treatable with diet or cofactorSmall molecule disease – amino acids, organic acids, fatty acid
Disorders of Energy Metabolism
Hypoglycemia, failure to thrive, lactic acidemia, hypotonia, myopathy, SIDSMitochondrial Disorders
Complex Molecules
Permanent and progressive symptomsLysosomal, peroxisomalFor Some Enzyme Replacement Therapies
Amino/Organic Acid DisordersDisorders of Intermediary Metabolism– Failure in breakdown pathways of amino
acids• Amino acid – Amine (NH2) = Organic Acid
– Examples of Amino acid disorders• PKU, Homocystinemia, Tyrosinemia
– Examples of Organic acid disorders• Methylmalonic acidemia, propionic acidemia
Amino Disorder Presentation
Generally non-acuteVarious symptoms dependent on disorder– Homocystinuria – thrombosis– Tyrosinemia – liver disease– PKU – hypopigmentation, seizures,
intellectual disability
Organic Acidemias
Neonatal presentation:– Uncomplicated pregnancy– Hypo or hypertonia– Feeding problems– Seizures– Lethargy– Unusual odors– Metabolic encephalopathy– Cerebral edema, coma, – Multi-organ failure and death
Lab Findings– Hypoglycemia– Metabolic acidosis– Hyperammonemia– Ketosis
Organic acids = Amino Acids with the Amine group (NH2) removed
PRESENTATION: Neonatal to Adult onset
Urea Cycle Disorders
Primary functions of Urea cycle:– elimination of waste nitrogen as urea to
avoid accumulation of toxic nitrogen compounds
– synthesis of arginine
Urea Cycle Disorders – Neonatal Onset
Lethargy by 48 - 72hrsVomitingHypothermiaTachypnea and apneaSeizuresCerebral edemaMetabolic alkalosisDeath
Urea Cycle Disorders - Late Onset
1 yr through adulthoodHyperammonemic
episodes confusion comaAssociated with change in diet,
illness (infection), surgery
Fatty Acid Oxidation Disorders
Fatty acid transport and mitochondrial oxidation plays major role in energy production→ times of fasting and metabolic stress
Presentation of FAOD
CardiomyopathyMyopathyEncephalopathySudden death
HypoketotichypoglycemiaElevated transaminasesElevated uric acidElevated CK
Full Term 4 Day OldA 4-day-old male is brought to an ER by his parents because of poor feeding
– Mother reports decreased feeding beginning on DOL # 3
– 2 episodes of vomiting on DOL # 3
– On DOL # 4, pt was less active, and went 6 hours without feeding or voiding
Birth History
Mother GBS+, all other labs negativeMother adequately treated with 2 doses of antibioticsROM = 12 hours, no maternal feverNSVD at 37 weeks gestationBW = 2.3 kg Discharged from nursery on DOL # 2Newborn screen sent on DOL # 2Formula feeding Q3 hours upon discharge
Physical Exam
Weight 2.0 kg (down 14% from BW)Length and HC: 50th percentileTemp=92o, BP=56/28, HR=120, RR=36Hypoactive infant with poor interactionAF sunken and dry mucous membranesNormal facies
Clinical CoursePatient became less responsive and developed worsening respiratory distressProgressed to cardio-pulmonary arrestResuscitated, and maintained on mechanical ventilation and vasoactive medicationsDeveloped seizure activity and was maintained on anticonvulsants
What are you thinking?
1. Sepsis2. Cardiac 3. Metabolic4. Inexperienced
parent
Sepsis
Cardiac
Meta
bolic
Inexperi
ence
d pare
nt
9%0%
91%
0%
What laboratory studies should you order?1. Blood Gas2. CBC3. Ammonia4. Electrolytes5. LFTs6. UA7. Lactic acid8. All of the above
Blood G
as
CBCAmmon
iaElec
trolyt
es
LFTs UA
Lacti
c acid
All of t
he ab
ove
0% 0% 0%
100%
0%0%0%0%
146 113 27 7.6 (Ca2+) 17.2 6.3 <5 2.4 38 (Gluc) 3.9 380
55.9
pH 7.13 pCO2 11 HCO3 <5 pO2 236
Lactate 0.8Ammonia = >1190
TP 5.6TP 5.6 AP 108AP 108Alb 3.1Alb 3.1 AST 50AST 50TB 12.4TB 12.4 ALT 36ALT 36UA: 5.5 / 1.025 /
2+ Ketones and Protein
What do we know…
Neonate in comaHypoglycemiaSevere metabolic acidosisHyperammonemiaKetonuria
Algorithm for the Diagnosis of the Neonate in ComaModified from Hoffmann et al, Inherited Metabolic Diseases, 2002
Blood: NH3 , pH, Electrolytes, Urine: Ketones
NH3
No AcidosisNH3 normalNo Acidosis
NH3 +/-Acidosis +Ketones ++Anion gap
Urea cycle defectHHH syndromeTransient hyperammonemia of the newborn
Organic acidemia (propionic, isovaleric, etc
Organic Acids
Organic AcidsAmino Acids
Amino acidemiaOrganic acidemia
Amino Acids
Treatment
AirwayCorrect dehydration and acidosisPrevent catabolism by providing calories (glucose at least 6 mg/kg/min; insulin if needed; intralipids)Stop potential toxins (Protein)Remove toxins (dialysis, activation of alternative pathways)Therapeutic cocktail (B12, folate, biotin, carnitine)Obtain urine and plasma for diagnostic testsCheck newborn screen results
Ogier de Baulny, H. Semin Neonatol 2002:7:17-26
Diagnosis?1. Fatty acid
oxidation disorder
2. Amino acidemia3. Organic
acidemia4. Mitochondrial5. Urea cycle
defect
Fatty a
cid oxid
ation d...
Amino acidem
ia
Organ
ic ac
idemia
Mitoch
ondrial
Urea cy
cle defe
ct
4% 8% 4%0%
83%
Further Studies Help Make the Specific Diagnosis
NBS contacted – increased C3 on screen – C3 elevation MMA, PA, Multiple CoA Carboxylase
DefAcylcarnitine profile confirmed elevated C3-carnitineUrine studies showed high levels of the following organic acids in his urine:• Methylcitrate which is formed from conjugation of
propionyl-coA with oxaloacetate– Propionylglycine, which results from conjugation of
propionyl-coA with glycine– Tiglylglycine, which results from incomplete isoleucine
catabolism
Diagnosis:
NBS reported elevated C3Differential: Propionic vs MethylmalonicacidemiaFINAL DIAGNOSIS: Propionic AcidemiaLong term treatment: restrict propiogenic amines (methionine, valine, isoleucine,threonine) by special diet; antibiotics to decrease gut bacteria
Case ReportA 2 year old child became unresponsive while A 2 year old child became unresponsive while traveling with her parents on the New Jersey traveling with her parents on the New Jersey Turnpike. Turnpike.
Initial treatment
EMS was called and took the child to the nearest emergency room where she was in coma and found to have pH of 6.9. – She was given IV hydration and
bicarbonate and transferred to the BMSCH
History
Mother and children flew into JFK on day of admission from Pakistan (18 hr flight). On the flight baby was given milk and juice. On arrival she was noted to be lethargic but family thought it was from the long travel.
Additional HistoryPast Medical History:– Born in Pakistan
Hospitalizations:– DOL 8 - persistent vomiting – 5 months - acidosis, apnea, bradycardia.
Intubated and treated with electrolyte solutions. When discharged parents told to give her ½ strength Good Start formula, no meat, no eggs or dairy.
Development: walking and talkingFamily Hx: Parents 1st cousins
Exam
Patient sedated and intubatedNormal faciesNo liver or spleen enlargementNo skin lesions
Initial labs on ArrivalpH 6.997pCO2 5.0 pO2 59 HCO3 1.2Na 146 Cl 112 HCO3 10 CA 8.9K 4.5 BUN 17 Glu 227Urine Ketones 2+NH4 37AST 32 ALT 17 Lactate 1.9
Anion Gap = Na+ - (Cl-+HCO3) Normal =10 +/- 4146 – (112+10) = 24
What do we know…
Acute episodic decompensationProlonged air flight – poor feeding, dehydration, high protein,
lactose+ feedParental consanguinitySevere metabolic acidosisRaised anion gap, ketone +Normal ammonia, lactate, LFT, glucose
Treatment
AirwayCorrect dehydration and acidosis – always D10 or higherPrevent catabolism by providing caloriesStop potential toxins (Protein)Remove toxins (consider dialysis, activation of alternative pathways)Therapeutic cocktail (B12, folate, biotin, carnitine)Obtain urine and plasma for diagnostic tests
Prolonged Hospital Course
Respiratory support - intubationHypotension requiring vasopressinSeizure-like activity – CT scan – large basal ganglia hypodensities, mildly enlarged ventricles
Diagnosis
Amino acids – essentially normalOrganic Acids – urine MMA very high
DX: METHYLMALONIC ACIDURIA Later testing showed:– CblA B12 responsive– mutation 433C>T (R145X) homozygote – a
common mutation in the MMA gene
Propionic and Methylmalonic Acidemia
Thymineuracilvalineisoleucinemethioninethreoninecholesterolodd chain fatty acids
Propionyl-CoA D-CH3 malonyl-CoA L-CH3 malonyl-CoA Succinyl CoA
Propionyl CoA Carboxylase
Methylmalonyl CoA racemase
Methylmalonyl CoA mutase
BIOTINADENOSYL
COBALAMIN (B12)
PROPIONIC ACID METHYLMALONIC ACID
Methylmalonic Acidemia
B12 Responsive Cobalamin Defects–– CblCbl A, B, H A, B, H -- faulty faulty
cobalamincobalamin synthesissynthesis–– CblCbl C, D, C, D, --
cobalaminecobalamine impaired impaired methyl and methyl and adenosylcobalaminadenosylcobalamin productionproduction
–– CblFCblF –– impaired impaired transporttransport
B12 Unresponsive Mutase defects–– Mut0 Mut0 –– no no mutasemutase
activityactivity–– MutMut++-- some some mutasemutase
activityactivity
A Case of CblC MMA/HCYsBefore treatment:
Neonatal Coma requiring ventilator support
With treatmentNo metabolic crisisGaining milestones
Metabolic Acidosis from IEMMetabolic Acidosis from IEM
Metabolic Acidosis
Anion Gap >16
+Hyperchloremia : GI losses, RTA, galactosemia,
NoNo
YesYes+Ketones
NoNo
+Hypoglycemia, Fatty acid oxidation defect
YesYes NormalNormal
AbnormalAbnormal ElevatedElevated
Amino & Organic Acids
Lactate/Pyruvate
Amino Aciduria
Organic Aciduria
Mitochondrial Energy Defect
NormalNormal
Hypoglycemia?
YesYesGlycogen Storage Disease, Gluconeogenesis defect
Pyruvate Dehydro- genase, Pyruvate Carboxylase
NoNo
Chart adapted from Dr. S. Lowe
When Should You Consider An IEM?Newborn period– Acute neurological decline
• Lethargy• Decreased feeding• Vomiting, diarrhea, dehydration• Seizures
Acidosis (especially if elevated anion gap)TachypneaHypo (or hyper) glycemiaHyperammonemia
Neonate’s response to severe illness
Respiratory distressHypotoniaPoor suckVomiting/diarrheaLethargy/Coma
Work-up of sick neonate
CXRCSFCulturesHead ultrasound
If the above are normal, in an infant who was initially well and then deteriorated, ….
THINK INBORN ERROR OF METABOLISM
Further Presentations
Up to the seventh decade of life“Recurrent syndromes”– Stupor, lethargy– Emesis; often with dehydration
Failure to thrive , poor feedingUnusual odors– Sweet (MSUD), sweaty feet, barn-like
Dystonia, choreoathetosis, myoclonus,hypotonia, unexplained seizuresHepatosplenomegalyMR or CP without a clear etiology
How Common Are IEM?1. More common
than childhood leukemia
2. Rare as hen’s teeth
3. Less than 1:10,000
4. Less than 1:20,000
More c
ommon
than
ch...
Rare a
s hen
’s te
ethLe
ss th
an 1:
10,00
0Le
ss th
an 1:
2000
0
20%
44%
32%
4%
How Common and Why?Individually rare but collectively numerous: 1:2500 newbornsGenetics– Most autosomal recessive– Few X-linked
Pathogenesis– Enzyme deficiencies– Cofactor binding
• problems with transport, absorption, enzyme action
Disease Incidence IEM Incidence Meningitis 1:3,700 Intermediary
Metabolism 1:4,000
Leukemia 1:10,000 PKU 1:10,000
Retinoblastoma 1:20,000 MMA 1:20,000
JRA 1:40,000 Galactosemia 1:35,000
CNS Tumor 1:42,000 Urea Cycle Defects 1:70,000
Chronic Renal Failure
1:100,000 MSUD 1:100,000
Incidence of Childhood Disorders vs. Inborn Errors of Metabolism
History and Physical Findings Suggestive of IEMHistory
Aversion to specific foodsUntoward reaction to childhood illnessesPsychomotor retardationGrowth failurePertinent family history-consanguinityEarly neonatal deaths
Physical FindingsRapid breathingExfoliative dermatitisSeizures and/or coma often with hypotoniaUnusual odorHepatomegalyCataractsMicrocephaly
ED Presentation
Review of 53 pediatric patients who presented to the ED and ultimately were diagnosed with IEM– 85% presented with neurological signs– 58% presented with GI complaints– 51% presented with both neuro and GI
Diagnostic approach to inborn errors of metabolism in an emergency unit.Pediatric Emergency Care. 16(6):405-408, December 2000.CALVO, M. MD, PhD; ARTUCH, R. MD, PhD; MACIA, E. MD; LUACES, C. MD, PhD; VILASECA, M. A. PhD; POU, J. MD, PhD; PINEDA, M. MD, PhD
Keep Your Index of Suspicion High for IEM
Obtain labs during acute episode– CBC with differential and platelets– Chemistries (lytes, ABG, Mg, Ca, LFT,
Glucose, ammonia, lactate, U/A with Ketones)
– Metabolic labs (amino acids plasma, urine, CSF?, plasma acylcarnitine, urine organic acids, urine acylglycine, urine orotic acid
– Freeze urine and plasma for further studies
Summer Camp EscapadeAn 8 year old went to sleep-away camp for the first time. After several days she became increasing lethargic and was brought to a local ED. On arrival she was barely arousable.
She was afebrile, with normal vital signs. The physical examination was unremarkable.
Laboratory studies were normal with the exception of ammonia which was 350.
Transferred to tertiary pediatric center
Suspected Diagnosis?
1. Tick-borne encephalitis
2. New onset seizure disorder
3. Reye Syndrome4. Urea Cycle Defect
Tick-born
e ence
phalitis
New onse
t seiz
ure d
i...Rey
e Syn
drome
Urea C
ycle
Defect
0%
100%
0%0%
Past Medical HistoryRecurrent episodes of vomiting as toddlerSoft neurological findings and learning disabilityHospitalized in infancy twice with gastroenteritis and dehydration. Took longer than usual to recoverLearning disabilityPicky eater – likes sweets and pasta, dislikes milk and meatAte more at camp due to policy of eat all foods on your plate and ask for more of what you like
Does this change your diagnosis? What other labs would you like to see?1. Amino acids2. Organic Acids3. Ketones4. Acylcarnitine
profile5. Amino acids and
organic acids Amino acids
Organ
ic Acid
sKeto
nes
Acylca
rnitin
e pro
file
Amino acids a
nd orga..
.
0%5%
71%
5%
19%
HyperammonemiaInherited Disorders
Urea cycle defectsDefects of urea cycle intermediate transport (HHH, LPI)Organic AciduriasFAOD
Acquired DisordersTransient hyperammonemia of the newbornReye SyndromeLiver FailureValproate therapyInfection with ureasepositive bacteriaLeukemia therapySevere systemic illness
Back to Patient: Additional Laboratory Studies
Amino acids – increased glutamine
Organic acids – increased oroticacid
Diagnosis: Partial Ornithinetranscarbamoylase deficiency (OTC)
The Urea Cycle
http://ureacycle.cnmcresearch.org/otc/
Urea Cycle Disorders - Neonatal Presentation
Normal at birthDevelop poor feeding, vomiting, lethargy, irritability, tachypnea after protein feed (about 24 hrs)Same presentation as SepsisRespiratory alkalosis Family history of unexplained neonatal death
Urea Cycle - Infantile Presentation to Adult
Variable anorexia, lethargy, failure to thrive, migraine/headacheMental status change after proteinSelf selected low protein dietNormal Developmental delayIrritability, behavior problemsIntermittent encephalopathy
OTC Deficiency
X-Linked Urea Cycle DefectIn Males – Severe defect neonatal coma
• massive hyperammonemia– Partial defect later onset
• variable hyperammonemia
In Females– May or may not be symptomatic depending on
Lyonization– Often avoid protein
Genetic Hyperammonemia Differential
ALKALOSIS primary urea cycle defect
ACIDOSIS organic acidemia, mitochondrial, lactic acidosis
HYPOGLYCEMIACARDIAC +/- FAODLIVER +/-,MUSCLE +/-
Treatment
Stop all protein intakeMaintain Anabolism – high glucose infusion with insulin (If FAOD not suspected add Lipid)Remove Ammonia – HemodialysisActivate alternate pathways – sodium benzoate, sodium phenylacetate, arginine/ citrulline (Ammonul)Correct acidosis, fluid and electrolyte balance
College Binge?
An 18 year old college student was brought to the ED disoriented. She had been at a prefinal party with friends where alcohol was served.Friends reported that she didn’t eat all day because she didn’t want to gain weight from the party. She got to the party had one drink and became disoriented and ataxic. They brought her to the ED. She swore she only had one drink.
Initial FindingsVital Signs: Pulse 100, Respiration 20, Blood pressure 70/20, Temp: 98.6
General: drowsy but arousable
Neuro: ataxic gait
CT scan (head) normal
Electrolytes: CO2 18 Anion gap 19
Uric acid=11.2
U/A neg.
Suspected Diagnosis
1. Alcohol intoxication
2. Drugs3. Post-ictal state4. IEM
Alcoho
l intox
icatio
n
Drugs
Post-ic
tal st
ate IEM
0%
96%
0%4%
Received a liter of NS with dextrose with improvement of BP and mental status
Blood alcohol – within legal limit
Tox screen - negative
What do we know?
Fasted Ataxia and stuporHypotensionAlcohol within legal limitNo glucose obtained initially but improved with glucose infusionAcidosis Increased uric acid
Assuming a metabolic disease is likely what tests should be ordered?
1. Acylcarnitine profile
2. Amino acids3. Porphyrins4. Purines and
pyrimidines
Acylca
rnitin
e pro
fileAmino ac
idsPor
phyri
ns
Purines
and p
yrimidines
13%21%
0%
67%
Tests you would order?
Acylcarnitine profile –increased C8
increased dicarboxylic acids (adipic, suberic, sebacic), hexanoylglycine
Consistent with MCAD deficiency
Urine Organic Acid –
FAOD
Hypoglycemia, lethargy, hepatomegaly, cardiomyopathy, liver failure, arrhythmiaLab Findings: no ketosis, ↑ CK, ↑ Uric AcidAcute Treatment: Glucose infusion 10-12 mg/kg/min til stable, thenContinuous enteral feeding low-fat, high glucose, normal proteinL carnitine 100 mg/kg/day (controversial and should be avoided in long chain disorders)
Chronic Treatment of Fatty Acid Oxidation Defect
Avoid fasting!!!Frequent carbohydrate mealsWhen ill institute emergency protocol– Oral hydration if possible (not vomiting,
good appetite)– IV D10 solution 1.5 x maintenance
May decompensate rapidly –err on the side of treatment
MCAD
Most common inherited disorder of fatty acid metabolismIf undiagnosed, mortality rate of 25%Autosomal recessive transmissionMCAD is necessary for mitochondrial beta-oxidation of fatty acids
MCAD Presentation
Classic presentationsSIDs/near-miss SIDsVomiting and lethargy after a period of fasting in a child 3-15 months of ageFew present after 4 years of lifeDecompensate from fasting, febrile illness, stressors (surgery), or alcohol consumption … triggers a Reye’s syndrome like illness
Newborn Screening Revolution
Tandem Mass Spectrometry (MS/MS)– Organic acidopathies– Amino acidopathies– Fatty acid metabolism
MS/MS: Sorts and counts…10
5
4
Newborn Screening: NJ 54 disorders by MS/MS & other technologies
Fatty acid oxidation disordersOrganic AcidemiasUrea Cycle DefectsAmino acid disordersBiotinidaseCAHCFGalactosemiaHemoglobinopathiesHypothyroidism
Sisters with propionic acidemia (www.savebabiescanada.org/FamilyStories/Jennaa)
Glutatic Acidemia I (www.savebabies.org/familystori
es/NikkiGA1.php)
LCHAD www.savebabiescanada.org/.../Andrew_
LCHAD.htm
General Emergency Management for Suspected IEM
Maintain ventilation and circulationAvoid catabolism – high glucose infusion 7-10 mg/kg/min (D10 1.5 X Maintenance)Stop intake of potential toxinCorrect ElectrolytesCorrect acidosisR/O Infection/treatConsult/Transfer Metabolic Center
Some Specific Management of Suspected IEM
Prevent catabolism – IV Glucose 7-10 mg/kg/min +/-intralipid 2 g/kg/d (if FAOD not suspected) Hyperammonemia Suspected Urea Cycle Defect– 250 mg/kg arginine over 90 min, then 250 mg/kg/d via
central line– 250 mg/g NaBenzoate/NaPhenylacetate (ammonul) load
IV over 90-120 min via central line, then 250 mg/kg/d– hemodialysis
Ketotic Hypoglycemia Suspected Organic Acidemia– 50 mg/kg levocarnitine IV loading; 50-100 mg/kg/24 hr– 1 mg B12 IM (hydroxy B12)– Biotin 10 mg PO
Hypoketotic Hypoglycemia Suspected FAOD– Avoid lipid– Avoid fasting– Provide glucose IV or enteral feeding
Toxin RemovalConsider for intoxication states (branch chain organic acidurias, urea cycle defects)Exchange transfusion – least effectivePeritoneal dialysis – 40-50 mg/kg dialysate, 15 min fill, 30 min dwell, 15 min drainage over 24-36 hrs. Simple but complicated by poor drainage, leakage of dialysate, risk of overhydrationHemodialysis – most effective
Vitamin CofactorsBiotin 10-20 mg/day Propionic, MCD, PC
Carnitine 50-100 mg po, 400 mg IV
100 mg po, iv
BCOA, Primary hyperammonemia, hyperlacticacidemiaFAOD
Cobalamin, B12 1-2 mg/day MMA
Folinic acid 10-40 mg/day Folinic acid responsive sx
Pyridoxine 50-100 mg/day Pyridoxine responsive sx
Riboflavin 20-40 mg/day Glutaric acidemia, FAOD
Thiamine, B1 10-50 mg/day MSUD, hyperlacticacidemia
HyperammonemiaLab findings: ammonia >400 μmol/l respiratory alkalosisMay have significant handicap despite treatmentTreatment:– Hemodialysis– High energy, protein-free nutrition– When NH3 < 150 add protein (iv amino acids)– Sodium benzoate 250 mg/kg load over 90-120 min
and 250 mg/kg/day; sodium phenylbutyrate 250 mg/kg load over 90-120 min and 250 mg/kg/day (Ammonul = 10% solution of above)
– L arginine 200 mg/kg/day iv– L-carnitine 400 mg IV
REMEMBER…. Inborn Errors of Metabolism Individually rare….but collectively numerous. Keep your index of suspicion high.