Metabolic Emergencies and their Management

James B. Gibson, MD, PhDDivision of Genetics and Metabolic Disorders

Department of Pediatrics, UTHSCSA

Dr.Muhammed .A. Jabbar NRC

Objectives

• Recognize common presentations of metabolic disease requiring immediate responses

• Know how to organize the first steps of the evaluation for metabolic disease

• Be able to direct initial management of the patient with suspected metabolic disease

• Know how to stabilize the patient with known metabolic disease

What are Metabolic Diseases• Inborn errors of biochemistry

• Frequency of 1/200 or less

• Detection: screening or symptoms

• Genetics: recessive, X-linked, mitochondrial, dominant

• May or may not be treatable

Clinical Presentations

• Neurological alterations, seizures, coma• Multiple organ system failure• Acidosis• Hyperammonemia• SIDS/ALTE• Failure to thrive• Hepatic or renal dysfunction• Malformations

• Organomegaly and coarsening of features

• Hematologic abnormalities

• Orthopedic concerns

• Developmental delays or regression

• Aggression

• Psychiatric symptoms

• Asymptomatic

Time of Initial Presentation

• Neonatal (<28 days of age)

• Infancy (1 month to 1 year)

• Childhood (over 1 year)

• Adolescence

• Adulthood

Differential Diagnosis in Sick Neonate

• Sepsis• Hypoglycemia• Congenital Cardiac Disease • Intracranial Bleed• Electrolyte Imbalance (Ca2+, Mg2+, Na+, K+, …)

• Endocrine Disease• Inborn Error of Metabolism• Syndrome (Dysmorphic/ Chromosomal Dx)• Toxin

Metabolic Approach to Sick Neonate

• Onset: Hours to Days• Poor Feeding• Vomiting• Hypotonia / Hypertonia• Tachypnea• Lethargy -- Stupor-- Coma• Unusual Odor (Urine, Breath, Skin, Cerumen)

• Seizures• Apnea

Approach to Sick Neonate

• Always consider the possibility of an inborn error of metabolism

• Initial tests: Blood gas, Anion gap, Glucose, Ketones, Ammonia, Lactate

• Stop protein feeds

• Give maximal calories from glucose• Secondary tests: plasma Amino Acids,

Lactate/pyruvate, Carnitine, Urine Organic Acids, Orotic Acid

Diagnostic Clues for Metabolic Diseases

• History– Family history– Feeding history– Past Medical history– Developmental history

• Physical Examination– Special clues in general examination– Neurologic signs

Dysmorphism in IEM• Head and Face

– Forehead high or big– Fontanel big anterior– Hair pattern– Eye

• wide spacing• cataracts or corneal clouding

– Ear placement low

• Genitalia– Hypospadius– Ambiguous genitalia / virilized

Other Malformations in IEM• Brain

– Heterotopias– Absence of corpus

callosum

• Kidney– Multicystic dysplasia

• Heart– Dilated cardiomyopathy– Hypertrophic cardiomyopathy

• Abnormal fat pads• Inverted nipples

Laboratory Findings in IEMs• Hypoglycemia

• Metabolic Acidosis

• Respiratory Alkalosis

• Ketosis

• Hyperammonemia

• Anemia, Leukopenia, Thrombocytopenia

• Urinary Reducing Substances

• Abnormal LFTs, Hyperbilirubinemia

• Inclusions in circulating WBCs

Critically ill infant: coma, intractable seizures, respiratory distress, cardiovascular collapse

Basic Lab tests: glucose, electrolytesarterial blood gas, ammonia, urinalysis

Major Abnormality

hypoglycemia metabolic acidosis

hyperammonemia no abnormality

Major Abnormality

hypoglycemia

hyperammonemia

Fatty acid oxidationDisorder of CHO metabolism

Critical samples Blood insulin, GH, cortisol3OHB/AcAc, FFA, lactateUrine organic acids, reducingsubstances

Urea cycle disorder

Critical samplesBlood amino acidsUrine orotic acids

Major Abnormality

metabolic acidosis

no abnormality

Critical samples

Critical samples

Blood amino acids, lactateUrine organic AcidsCSF lactate, neurotransmitters

Organic aciduria, NKH, Sulfite oxidase,Pyridoxine responsive seizure,Neurotransmitter disease

**ketosis (DNPH) MSUD

Blood amino acidsUrine organic Acids

Blood amino acids, lactateUrine organic AcidsCSF lactate

Critical samples

Organic aciduria, lactic acidoses

Hyperammonemia

• Normal ranges– Newborn 64 - 107 micromol/L– Adult 13 - 34 micromol/L

• Acute hyperammonemia: progression of combativeness to lethargy to coma to death

• Neonatal Presentation– Lethargy, anorexia, vomiting, apnea, seizures, coma

• Acute, catastrophic; often fatal

• Infantile (subacute)– FTT, developmental delay, seizures, ataxia, hepatomegaly,

cerebral atrophy– Stress/fever/catabolism-induced episodic

Sx Low pH Ketosis Lactate NH3 Glu Possible DX

Neuro 0 ++ 0 0 N MSUD

Neuro + ++ 0 + N Organic acidemia

Neuro ++ + ++ 0 N,D Lactic acidemia

Neuro 0 0 0 ++ N Urea Cycle

Neuro 0 0 0 0 N NKH, ETC, Peroxisomal

Liver + + + 0 D GSD

Liver Heart

+ 0 0 0 D FAO Defect

Modified from J-M Saudubray, 2001 MMBID

Urea Cycle Disorders• Encephalopathy (progressive), hyperpnea• Hepatopathy and hyperammonemia

• No to minimal acidosis• Glucose and CBC normal• Lactate normal to increased

• Neonatal illness– Hyperammonemia, coma, cerebral edema

• Illness in older patients– Recurrent presentation like neonatal illness– Vomiting, abnormal liver enzymes, episodic

hepatomegaly with ataxia, Reye syndrome, psychiatric illness

Urea Cycle Enzyme Defects

• Immediate work-up– Plasma amino acids– Urine orotic acid

• Other evaluation– Enzyme/DNA studies– Liver tissue

• Autosomal recessive– Except ornithine transcarbamylase

deficiency (OTCD) which is X-linked

Ammonium+ + bicarbonate + ATPCarbamyl Phosphate

SynthaseCARBAMYL PHOSPHATE

OrnithineTranscarbamylase

ArgininosuccinateSynthase

Arginase

Aspartate

UREA

Fumaricacid

CITRULLINE

ORNITHINE

ARGININOSUCCINIC ACID

ARGININE

ArgininosuccinateLyase

Encephalopathy & Ketones

• Normal lactate and glucose, • Ammonia normal to increased• Keto-acids present (+ DNPH)• Odor in urine or cerumen• Alternating hyper- and hypotonia• Cerebral edema, seizures

• Maple Syrup Urine Disease– Branched chain ketoacid dehydrogenase

defect

• Plasma amino acids– Urine organic acids

Sx Low pH Ketosis Lactate NH3 Glu Possible DX

Neuro 0 ++ 0 0 N MSUD

Neuro + ++ 0 + N Organic acidemia

Neuro ++ + ++ 0 N,D Lactic acidemia

Neuro 0 0 0 ++ N Urea Cycle

Neuro 0 0 0 0 N NKH, ETC, Peroxisomal

Liver + + + 0 D GSD

Liver Heart

+ 0 0 0 D FAO Defect

Encephalopathy, Acidosis and Ketosis

• Increased anion gap• NH3 may be moderately increased• Lactate normal to increased• Glucose may be normal to increased• Calcium normal to decreased• Leucopenia or Thromocytopenia

• Organic acidemias– Or ketolytic defects

• Urine organic acids & Carnitine, AcylcarnitineProfiles

Sx Low pH Ketosis Lactate NH3 Glu Possible DX

Neuro 0 ++ 0 0 N MSUD

Neuro + ++ 0 + N Organic acidemia

Neuro ++ + ++ 0 N,D Lactic acidemia

Neuro 0 0 0 ++ N Urea Cycle

Neuro 0 0 0 0 N NKH, ETC, Peroxisomal

Liver + + + 0 D GSD

Liver Heart

+ 0 0 0 D FAO Defect

Prototypical Organic Acidemias

• Propionic acidemia (carboxylase)– Propionyl-Co A inhibits other systems

• PDH complex; N-acetyl-glutamate synthase; glycine cleavage system

• Isovaleric acidemia (dehydrogenase)• Methylmalonic Acidemia (mutase)• Treatment

– Low amino acid diet and carnitine– Glycine, thiamine, cobalamin or biotin in some

cases– Hydration– Metronidazole?

Diagnosis of Organic Acidemias

• Traditional– Urinary Organic Acids by GC/MS– Enzyme Analysis

• Dried Filter Paper Urine Sample – Stable isotope dilution GC/MS– Sample stable for two weeks– Potential use in neonatal screening

• Proton NMR spectroscopy– Use of underivitized material

• MS/MS from Dried Blood Spots

ODOR COMPOUND DISORDERMaple syrupsweet

Isoleucine metabolites Maple Syrup Urine Disease

Musty Phenylacetic acid Phenylketonuria (PKU)

Sweaty feetCheesy

Isovalerate Isovaleric AcidemiaGlutaric Aciduria, type II

Cabbage a-Ketomethylbutyrate Tyrosinemia, type IHypermethionemia

Tomcat’s Urine

Methylcrotonic acid Methylcrotonic AcidemiaMultiple Carboxylase Deficiency

Fishy TrimethylamineCarnitine

Trimethylaminuria

Oasthouse a-Hydroxybutyric acid Methionine malabsorption

Metabolic Acidosis: Lactate• Encephalopathy• May have no normal period after birth

• Acetone normal to increased• Anion gap increased

• Glucose and NH3 normal to decreased

• Pyruvate dysmetabolism, TCA cycle and Respiratory chain defects

• Labs– Lactate/pyruvate– Quantitative ketones– Urine organic acids– Enzyme studies

Krebs Cycle

CarbohydrateCarbohydrateProteinProtein

Fat

AlanineAAT

PC

GlucoseGlucose

Lactate

Ketones

Fatty Acids

Acetyl CoA

Succinate

Pyruvate

Oxaloacetate

PEP

LDH

PDH

Leucine Valine

Isoleucine

Propionate

MethylmalonateUrea cycleUrea cycleNHNH44

ATP

ETC

NADH NAD

Succinate Fumarate

H+

H2OO2½

I IV V

II

IIICoQ

CytoC

Matrix

Intermembrane Space

e-

ADP + Pi ATP

H+

Lab Tests• Lactate and Pyruvate

– Cytoplasmic redox state– Normal ratio: 10-20

• Low ratio, even if normal concentrations: PDH• 3-Hydroxybutyrate/Acetoacetate (Ketone bodies)

– Mitochondrial redox state

• High L/P ratio >30; postprandial ketonemia and normal ketone ratio(<1.5) PC/ KGDD

• High L/P ratio >30 (and ketone ratio>2.0)

Respiratory Chain Defects

Lactic Acidoses• May need more than one set of labs• Subset of disorders with lactate increased by

feeding• GSD 1, PDH, PC, certain respiratory chain defects,

Multiple Carboxylase Defects, KGDD

• Other diseases show highest lactate after fasting

• GSD III/VI, Glycogen synthase, FAOD & Fructose diphosphatase

• Permanent– Neurologic signs or >10mM Congenital LA

– Hypoglycemia and Hepatomegaly GSD I

Lab Testing for ETC Defects

• Blood (may need fasting and fed samples)– Lactate, pyruvate, -hydroxybutyrate,

acetoacetate, plasma amino acids– ? Forearm ischemia or treadmill tests

• Urine: organic acids, amino acids• CSF: lactate, pyruvate, ?neurotransmitters• Fibroblasts and Muscle for enzymology

– can use other organs with controls

• DNA studies: blood, muscle, other organs

Acidosis and Hypoglycemia• Acetone, Ketones negative

• NH3 and lactate normal to increased

• Hepatic or cardiac symptoms• Seizures with hypoglycemia

• Fatty acid oxidation defects• Ketogenesis defects

– ? Respiratory chain defects

• Organic Acids &

Carnitine, Acylcarnitine

Profiles

Sx Low pH Ketosis Lactate NH3 Glu Possible DX

Neuro 0 ++ 0 0 N MSUD

Neuro + ++ 0 + N Organic acidemia

Neuro ++ + ++ 0 N,D Lactic acidemia

Neuro 0 0 0 ++ N Urea Cycle

Neuro 0 0 0 0 N NKH, ETC, Peroxisomal

Liver + + + 0 D GSD

Liver Heart

+ 0 0 0 D FAO Defect

LC acyl-CoALC acylcarnitine

LC acyl-CoA

MC acyl-CoA

C10-C24 (26) L-Carnitine C4-C8(9/10)

Plasma Plasma MembraneMembrane

OMMOMM

IMMIMM

L-Carnitine

FABP

CoASH

LC acylcarnitine

L-Carnitine

CoASH

-oxidation spiral

CoASH

AASS

CTCT

CPT 1CPT 1

CPT 2CPT 2

TRANSTRANS

ASAS

Acyl-CoA 2,3-Enoyl-CoA

3-hydroxyacyl-CoA3-Oxoacyl-CoA

Acetyl-CoA

FAD FADH

NADNADH

H2O

Acetoacetyl-CoA

HMG-CoA

Acetoacetate

3-Hydroxybutyrate

(R-CHCH22-CH-CH22-CO-SCoA) (R-CH=CHCH=CH-CO-SCoA)

OHOH II(R-CH-CHCH-CH22-CO-SCoA)(R-C-CHC-CH22-CO-SCoA)

OOIIII

11

2244

33

5566 77

CoASH

MCAD Signs and Symptoms

Symptom/sign Percent Affected Lethargy 84 Emesis 66 Encephalopathy 49 Respiratory arrest 48 Hepatomegaly 44 Seizures 43 Apnea 37 Cardiac arrest 36 Sudden Death 18

Iafolla et al ., J Pediatr 124:409-415, 1994

Treatment of FAO Disorders

• Depends on the Fatty Acid Oxidation Defect• Vitamin/Cofactors

– Carnitine– Riboflavin

• Diet manipulation– Avoiding fasting– Low fat diet High carbohydrate diets– MCT oils V Long Chain AcylCoA Defects/LCAD

• Transplantation???• Prevention of intercurrent illness

– Immunizations– Avoiding ill contacts

• Triheptanoate??

The 2:00 AM approach to hypoglycemia

• Age of patient

• When did this occur - first time or repeat

• Why– Over-utilization– Underproduction– Both?

• Stop the hypoglycemia!!

ED Work-up

• Prioritize: New problem? Critical patient? Seizing/Combative/Unresponsive?

• Glucose– <40mg/dl (or <60 mg/dl and symptomatic)

• Get: Cortisol, insulin, growth hormone, lactate/pyruvate and ABG

• Also get ED7, AST, ALT, GGT, ammonia, quant. ketones (-OH butyrate and acetoacetate), plasma amino acids, acylcarnitine profile, free fatty acids

• Urine: UA, organic acids and amino acids

Blo

od

Glu

cose

co

nce

ntr

atio

n m

g/d

LB

loo

d G

luco

se c

on

cen

trat

ion

mg

/dL 70 Catecholamine and Glucagon SecretionCatecholamine and Glucagon Secretion

Cortisol and Growth Hormone Secretion

40

30

20

10

0

60

50Autonomic SymptomsAutonomic Symptoms

Neuroglycopenic Symptoms & Neuroglycopenic Symptoms & Cognitive DysfunctionCognitive Dysfunction

LethargyLethargy

Seizures and ComaSeizures and Coma

Hypoglycemic Signs and symptomsHypoglycemic Signs and symptoms

When they crash = Why they crashed

• Fasted for: <1 hr– Hyperinsulinism

• 1-6 hrs– GSD 1,

gluconeogenesis

• 8-24hrs– Fatty acid oxidation– CPT I

(infants/young child)

– Low free fatty acids (FFA); High insulin (hyperammonemia)

– High FFA with lactic acidosis

– High FFA with organic aciduria, abnormal ketone quantitation, abnormal acylcarnitines, low carnitine concentration

Neonatal Hypoglycemic Metabolic Disease

• Fatty acid oxidation defect– Acidosis: – to ++– Ketosis: NO– Ammonia: +/- to ++– Lactate: +/- to ++

• Glycogenosis/Fructose diphosphatase– Ammonia : normal to +– Ketones: +– Lactate +/++– Ketones: - in type 1; ++ type 3 GSDs– Other: uric acidemia, elevated triglycerides or

cholesterol

Neonatal Hypoglycemic Metabolic Disease continued

• Liver failure?– Newborn screen?– Galactosemia

• NH3 nl to +• No to + acidosis or ketosis• Lactate + to ++

– DDX • Tyrosinemia I, neonatal hemochromatosis,

fructosemia, respiratory chain disorders

Non-neonatal Hypoglycemia

• Fatty acid oxidation defects

• Respiratory chain disease

• Hereditary fructose intolerance

• Organic acidemias

• Gluconeogenic defects– Fructose diphosphatase, glucose 6-

phosphatase, glycogen synthase

Metabolic Diseases Can Present as Hypoglycemia 2

Hepatomegaly– Permanent

• Severe liver failure• Cirrhosis• Isolated

hepatomegaly

– Without• Ketoacidosis• Acidosis without

ketosis• Ketosis without

acidosis• Without ketosis

Example

• Tyrosinemia I• Fructose Intolerance• PEPCK and GSD III,

fructose diphosphatase

• organic aciduria• HMG-CoA lyase and

rarely FAO defect• Hyperketotic

hypoglycemia• Typical FAOD

Cardiomyopathy in Infants

• Lysosomal (storage) disorders

• Mitochondrial disorders

• Amino acidopathies

• Organic acidemias

• Fat dysmetabolism and / or carnitine deficiencies

Seizures

• Biochemically quiet:• No acidosis; normal lactate, ketones, glucose and NH3

– Non-ketotic hyperglycinemia– Sulfite oxidase/ xanthine oxidase– Pyridoxine dependency– Peroxisomal disorders– Glucose transporter defect– Trifunctional protein defect

• CSF glucose & glycine, pAA, VLCFA, Sulfites, Trial of pyridoxine

Nonketotic Hyperglycinemia

• Lethargy, hypotonia, seizures; characteristic EEG, apnea

• Defect in glycine cleavage • Glycine is a neurotransmitter

– Classic glycine receptors are inhibitory– Excitatory neurotransmitter of the N-methyl-

D-aspartate receptor by allosteric modulation of receptor activity

• Leads to overstimulation of the pathways and damage

Won’t Newborn Screening Solve This?

• Newborn screening is expanded– But only 28 disorders in Texas

• NBS may not give an answer until after the infant is ill– Critical window of time – Turn-around is not fast enough

• NBS will detect– most of the severe or moderate cases of screened

disorders

• NBS will not detect– non-screened disorders– all mild cases of a disorder (later presentations)

Newborn Screening is not….

• Enough for a diagnosis– False positives will occur

• Abnormal analyte but no disease

• Fail-safe– False negatives will occur

• No abnormality for a screened disorder

• As complex to interpret as you thought

• Physicians must still recognize & treat the infant with an IEM

• 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC)

• 3-OH 3-CH3 glutaric aciduria (HMG) • Argininosuccinic acidemia (ASA) • Beta-ketothiolase deficiency (BKT) • Biotinidase deficiency (BIOT) • Carnitine uptake defect (CUD) • Citrullinemia (CIT) • Congenital adrenal hyperplasia

(CAH) • Congenital hypothyroidism

(HYPOTH) • Cystic fibrosis (CF) • Galactosemia (GALT) • Glutaric acidemia type I (GA I) • Hb S/Beta-thalassemia (Hb S/Th) • Hb S/C disease (Hb S/C)

• 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC)

• 3-OH 3-CH3 glutaric aciduria (HMG) • Argininosuccinic acidemia (ASA) • Beta-ketothiolase deficiency (BKT) • Biotinidase deficiency (BIOT) • Carnitine uptake defect (CUD) • Citrullinemia (CIT) •

• • • Cystic fibrosis (CF) • • Glutaric acidemia type I (GA I) • •

• Hearing loss • Homocystinuria (HCY) • Isovaleric academia (IVA) • Long-chain L-3-OH acyl-CoA

dehydrogenase deficiency (LCHAD) • Maple syrup urine disease (MSUD) • Medium chain acyl-CoA dehydrogenase

deficiency (MCAD) • Methylmalonic acidemia (Cbl A,B) • Methylmalonic acidemia (mutase

deficiency) (MUT) • Multiple carboxylase deficiency (MCD) • Phenylketonuria (PKU) • Propionic acidemia (PROP) • Sickle cell anemia (SCA) • Trifunctional protein deficiency (TFP) • Very long-chain acyl-CoA

dehydrogenase deficiency (VLCAD)

• Tyrosinemia type I (TYR I)

• Hearing loss

• Phenylketonuria (PKU) • Sickle cell anemia (SCA)

ACMG/March of Dimes List of 29 Disorders for NBS

‘New’ Disorders - New Technology

• Expanded group of amino acid diseases– Phenylketonuria– Argininosuccinic acidemia (ASA) – Citrullinemia (CIT) – Homocystinuria (HCY) – Tyrosinemia type I (TYR I) – Maple syrup urine disease (MSUD)

• New group of Organic Acid Disorders• New group of Fatty Acid Oxidation Disorders

• New / expanded group of Miscellaneous / Other Screened Disorders

Interpreting a NBS report

• Added sections• Amino acids

– Normal or named elevations– Possible disorder listed

• Acylcarnitine profile– Identify the abnormal chemical species– Possible disorders listed

• Biotinidase

What to do

• Algorithmic approach

• Even a short delay may harm an infant

• Follow the ACT sheet and algorithm– Find the patient– Evaluate the patient– Obtain labs– Speak with a metabolic geneticist

What Analyte

PCP’s Actions

DiagnosticEvaluations

Clinical Snapshot

More Information

DSHSACT Sheets

Confirmatory Testing

• Some values will be very high– Metabolic Emergencies requiring immediate

admission• Intravenous fluids• May require specialized medications

• Many values will require repeat testing, or– Acylcarnitine profile– Urine organic acids– Plasma amino acids– Ammonia– Urine Orotic Acid

Flow Sheet format

Algorithms

Actionsin shaded boxes

Results in Unshaded box

Plasma AC (C8) – highUrine OA – Normal/high dicarboxylic acids

Urine AG – high hexanoylglycine

MCAD Deficiency

http://www.acmg.net/resources/policies/ACT/condition-analyte-links.htm

Newborn Screening Directory 1-800-252-8023

• Case Management Extensions• General Information 2129• Congenital Adrenal Hyperplasia (CAH) 2819• Congenital Hypothyroidism 3666• Galactosemia 6827• Hemoglobinopathies 6832• Phenylketonuria (PKU) 6827• Biotinidase Deficiency 2071• Fatty Acid Disorders, Organic Acid Disorders,

Amino Acid Disorders 7715

Emergency Medications

• Dextrose– 10% at a rate of 1.5 x maintenance provides a GIF

high enough to suppress most catabolism • Alkali

– Sodium bicarbonate to treat acidosis• Ammonia trapping agents

– IV = Ammonul®• Combination of sodium benzoate and sodium

phenylacetate• Needs central line

– Enteral = sodium phenylbutyrate (Buphenyl®)

Emergency Therapies

• Dialysis– Needed for extreme hyperammonemia– For organic acidemias– To bring amino acid levels down– Peritoneal vs. hemodialysis/hemofiltration

• Carnitine– IV 100 – 200 mg/kg/day– Side effects in large oral doses– Caution in long chain fatty acid defects

Vitamin Therapies

• Pyridoxine (Vitamin B6) 100 mg– Biochemically quiet seizures– Homocystinuria

• Biotin 10 mg enterally– Biotinidase defect– Holocarboxylase synthase– Pyruvate carboxylase

• Cobalamin (Vitamin B12)– Methylmalonic acidemia with hyperhomocysteinemia

• Mitochondrial disease– Niacin, Riboflavin, Coenzyme Q10, Vitamin E, Vitamin C, ++

+

Patient Known to Have Metabolic Disease?

Urea Cycle DefectFatty Acid DefectOrganic AcidopathyLactic AcidosisGlycogen Storage

HypoketosisHypoglycemiaHyperammonemiaIncreased Anion GapMetabolic Alkalosis

Notify Metabolic MD

Yes No ABGNH3GlucoseKetonesLactate

StorageDisorder

UnchangedVS?

Respiratorypattern/rates

EmesisCNS status

Physical Exam

Treatment plan known?

? Intubate

No Diagnosticalgorithm

Emergency Rx Plan

NoYesFollow Plan

Add common sense care

No

CNS Status

?Toxins?IEM

Improved

Type Known ?Yes

Yes

Other lab studies

D10+ IVFAnd if￪ NH3 NH3 Trapping AgentAcidosis NaHCO3

Seizures Anticonvulsant Carnitine

Summary

• Consider IEM in your DDX of a sick child• Five basic lab studies for acute diseases

– Second group of labs often needed

• Treat with glucose– And correct metabolic derangements

• Special medications for certain disorders• Known patients may get ill

– Fluids, carbohydrate calories and correction of physiologic derangements

• Call for help

Some materials in this talk were prepared using resources provided

by the Carlie Herndon Memorial Fund

ODOR COMPOUND DISORDER Maple syrup sweet

Isoleucine metabolites Maple Syrup Urine Disease

Musty Phenylacetic acid Phenylketonuria (PKU)

Sweaty feet Cheesy

Isovalerate Isovaleric Acidemia Glutaric Aciduria, type II

Cabbage a-Ketomethylbutyrate Tyrosinemia, type I Hypermethionemia

Tomcat’s Urine

Methylcrotonic acid Methylcrotonic Acidemia Multiple Carboxylase Deficiency

Fishy Trimethylamine, Carnitine

Trimethylaminuria

Oasthouse a-Hydroxybutyric acid Methionine malabsorption