1 metabolic disorders inborn errors of metabolism dr. abdullah alomair mb chb, mrcp (edin), frcp...
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Metabolic Disorders
Inborn Errors Of Metabolism
DR. ABDULLAH ALOMAIR
MB ChB, MRCP (Edin), FRCP (Edin.), DCH (Glas.)
Associate Professor of PediatricsConsultant PediatricianDepartment of Pediatrics
PRESIDENT SAUDI PEDIATRIC ASSOCIATION
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Inborn Errors Of Metabolism (IEM) -A large group of hereditary biochemical diseases.-In autosomal dominant disorders, the structural abnormality dominates over the chemical abnormality. -Specific gene mutation cause abnormal or missing proteins that lead to altered function.
Metabolic Disorders Metabolic Disorders
Inborn Errors Of MetabolismInborn Errors Of Metabolism
SINGLE GENE DEFECTS in synthesis or catabolism of proteins, carbohydrates, or fats.
Defect in an ENZYME or TRANSPORT PROTEIN , which results in a block in a metabolic pathway.
EFFECTS :
- toxic ACCUMULATION of substrates before the block,
- intermediates from ALTERNATIVE pathways
- defects in ENERGY production and utilization caused by a deficiency of products beyond the BLOCK.
Every metabolic disease has several forms that vary in AGE OF ONSET , clinical severity and, often, MODE OF INHERITANCE.
Pathophysiology
Classification
Transient Hyperammonemia of Newborn
Inborn Errors of Metab:• Organic Acidemias • Fatty Acid Oxidation def• Urea Cycle Defects• Amino Acidurias• Non-ketotic Hyperglycinemia
Molybdenum Cofactor Deficiency
• Sulfite Oxidase Deficiency Metal Storage Disorders: Cholesterol Disorders: Leukodystrophies, other…
• Krabbe disease
Mitochondrial Disorders Glycogen Storage Disorders Hyperinsulinism Carbohydrate Disorders Lysosomal Disorders
• Mucopolysaccharidoses (X-linked Hunter’s, Hurler’s)
• Gaucher disease• Tay-Sachs Disease
Peroxisomal Disorders• Zellwegger’s (Cerebro-
Hepato-renal)• X-linked
Adrenoleukodystrophy
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Metabolic Disorders• Due to inherited reduced activities of proteins
involved in the synthesis, breakdown or transport of amino acids, organic acids, fats, carbohydrates and complex macromolecules.
• Most are autosomal recessive due to mutations that result in reduced enzyme activity or reduced amount of enzyme.
• Pathogenesis may include: accumulation of a toxic intermediate, reduced amount of a necessary end product or activation of an alternate pathway.
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Metabolic Disorders
From history:
Parental history :
Consanguineous parents
Previous unexplained neonatal deaths
Particular ethnic group (in certain diseases)
Features suggestive of metabolic disorder :
Features suggestive of metabolic disorder :
Metabolic Disorders Metabolic Disorders
Examination findings:
Organomegaly (e.g. hepatomegaly) in the absence of viral infection.
Cardiac disease
Ocular involvement (e.g. cherry red spot)
Skin manifestations e.g. pigmentations.
Unusual odour. Due to change in the chemicals of the urine.
Non-specific neurological findings. In a non-meningitis child you have to think of metabolic disorders.
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Neonatal and Post Neonatal Presentation
Neonatal presentationNormal-appearing child at birth (some conditions are associated with dysmorphic features)
• poor feeding• lethargy• vomiting• seizures• coma• unusual odour• Hypoglycaemia is very dangerous, acidosis (in some
defects)
Neonatal and Post Neonatal Presentation
Post neonatal presentation
• Encephalopathy without the presence of infection.
• Developmental regression• Reye syndrome ( damage of the brain and
liver eventually leading to encephalopathy).
• Motor deficits• Seizures• Intermittent episodes of vomiting, acidosis,
hypoglycaemia and/or coma triggered by
stress e.g. infections, surgery.
Newborn Screeningthe earlier its detected the fewer the complications
PKU - in NICU even if not advanced to full feeds Galactosemia Hypothyroidism Hemoglobinopathies Biotinidase defic, CAH (21-OH’ase def), Maple syrup urine disease ( MSUD )
- GUTHRIE TEST: it’s a cheap test that requires only one drop of blood to check for multiple metabolic disorders.
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Specific Tests:
• Direct biochemical assays of metabolites or their metabolic by-products, or of an enzyme’s function.
• DNA studies
• Neuro-radiology
PROCEDURES FOR DIAGNOSIC CONFIRMATION
Non – Specific Tests:
• Blood glucose, ammonia, bicarbonate and pH
• Peripheral Blood smear – WBC or bone marrow vacuolization , foam cells or granules.
• C.S.F. glycine , other amino acids , lactate. Amino acids shouldn’t be present in the CSF if its there it indicates a metabolic disorder.
Bone marrow transplantation is a treatment of both inborn errors of metabolism
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Inborn Error of MetabolismInborn Error of Metabolism Urine OdorUrine Odor
Gultaric AcidemiaGultaric Acidemia Sweaty feetSweaty feet
Maple Syrup urine diseaseMaple Syrup urine disease Maple syrupMaple syrup
HypermethioninemiaHypermethioninemia Boiled cabbageBoiled cabbage
PhenylketonuriaPhenylketonuria Mousy or mustyMousy or musty
TrimethylaminuriaTrimethylaminuria Rotten fishRotten fish
INBORN ERRORS OF AMINO ACID METABOLISM ASSOSIATED WITH ABNORMAL ODOR
They may come with flattened mid-face, indistinct philtrum, low nasal bridge and single palmar crease.
Small chin is called micrognathia
Low-set ears: >1/3rd of the ears lower than the line connecting the 2 pupils.Low nasal bridge: common sign, which is also seen in Down.
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Genetic:
Establish diagnosis.
Carrier testing.
Pedigree analysis, risk counseling.
Consideration of Prenatal diagnosis for pregnancies at risk.
MANAGEMENT OF IEMMANAGEMENT OF IEM
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Family counseling and support.
Education to promote increased compliance with special form of therapy such as Protein – restricted diet.
Assessment of community resources and support groups.
PSYCHOSOCIAL , EDUCATIONAL , FAMILIALPSYCHOSOCIAL , EDUCATIONAL , FAMILIAL
MANAGEMENT OF IEMMANAGEMENT OF IEM
TREATMENT OF GENETIC DISEASES
• Modify environment, e.g., diet, drugs
• Avoid known environmental triggers
• BMT• Surgical, correct or repair defect or organ transplantation
• Modify or replace defective gene product, megadose vitamin therapy or enzyme replacement
• Replace defective gene
• Correct altered DNA in defective gene
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Galactosemia
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: Carbohydrates
GalactosemiaEnzyme deficiency: Galactose-1-phosphate uridyl transferase deficiency.
It is a rare autosomal recessive.
● Follows feeding with lactose containing (breast milk / formula) ● Patient feeds poorly , have vomiting, jaundice, hepatomegaly and
hepatic failure● Chronic liver disease● Cataracts● Developmental delay develop if condition is untreated., if they were
given galactose free diet you will avoid the social and mental damage but they might complain of dyslexia.
CYSTIC FIBROSIS
Cause : Loss of 3 DNA bases in a gene for the protein that transports Cl ions so salt balance is upset. Causes .a build up of thick mucus in lungs and digestive organs. It is diagnosed by sweat test: measuring the chloride concentration in the sweat
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AMINO ACID DISORDERS
Phenyl Ketonuria (PKU)
Phenylalanine TyrosineHydroxylase
Phenylalanine
Phenyl ethylamine Phenyl pyruvic acid
Phenyl pyruvic acid is what gives the urine its smell because its ketonic and acidic.
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Phenylketonuria PKU
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1. Hyperactivity, athetosis, vomiting.
2. Blond.
3. Seborric dermatitis or eczema skin.
4. Hypertonia.
5. Seizures.
6. Severe mental retardation.
7. Unpleasant odor of phenyl acetic acid.
PKU PKU
DIAGNOSISDIAGNOSIS
• Screening : Guthrie Test.
• High Phenylalanine > 20 mg/dl.
• High Phenyl pyruvic acid.
TREATMENTTREATMENT
• DIET.
• BH4 (Tetrahydrobiopterin).
• L – dopa and 5- hydroxytryptophan.
CLINICAL CLINICAL FEATURES FEATURES
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PKU
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Albinism
Iris had fibrous tissue, and it’s colourless and is red due to vessels.
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Homocystinuria
Elevated homocystine levels affect collagen , result in a Marfanoid habitus, ectopia lentis but lens dislocation in homocystinemia is downward unlike in marfan its upward, mental retardation and strokes, its harmful to the bones and body. Araachnodyctly.
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METHIONINE CYSTATHIONINE
Homocystinuria
Cysathionine
Synthatase
DIAGNOSIS:
High methionine and homocystine.
TREATMENT:
•High dose of B6 and Folic Acid.•Low methionine and high cystine diet,•Betain (trimethylglycine)
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Homocystinuria
Amino acid disorders :Urea cycle defects and hyperammonemia
All present with lethargy, seizures, ketoacidosis, neutropenia, and
hyperammonemia
Ornithine carbamyl transferase (OTC) deficiency
Carbamyl phosphate synthetase deficiency
Citrullinemia
Arginosuccinic Aciduria
Argininemia
Transient tyrosinemia of prematurity
First Steps in Metabolic Therapy for IEM
• Reduce precursor substrate load
• Provide caloric support
• Provide fluid support
• Remove metabolites via dialysis
• Divert metabolites
• Supplement with cofactor(s)
Therapeutic Measures for IEM
• D/C oral intake temporarily• Usually IVF’s with glucose to give 12-15
mg/kg/min glu and at least 60 kcal/kg to prevent catabolism (may worsen pyruvate dehydrogenase deficiency)
• Bicarb/citrate Carnitine/glycine• Na Benzoate/arginine/citrulline• Dialysis--not exchange transfusion• Vitamins--often given in cocktails after labs
drawn before dx is known• Biotin, B6, B12, riboflavin, thiamine, folate
Important IEM Treatment supplements:
• Carnitine for elimination of Organic Acid through creation of carnitine esters.
• Sodium Benzoate, phenylacetate and phenylbutyrate for Hyperammonemia elimination.
CARNITINE METABOLISMCARNITINE METABOLISM
• An essential nutrient found in highest concentration in red meat.
• Primary function : Transport long-chain fatty acids into mitochondria for oxidation.
• Carnitine supplementation in fatty acid oxidation disorders and organic acidosis may augment excretion of accumulated metabolites , but may not prevent metabolic crises in such patients .
• Carnitine is an endogenous metabolite but can be given as supplementations.
CARNITINE METABOLISM
• Primary defects of carnitine transport manifest as Reye syndrome , cardiomyopathy or skeletal myopathy with hypotonia
• Secondary carnitine deficiency is due to diet ( esp. I.V alimentation or ketogenic diet ) , renal losses , drug therapy ( esp. valproic acid) and other metabolic disorders ( esp. disorders of fatty acid oxidation and organic acidemias )
• Prognosis depends on the cause of the carnitine abnormality.• Free and esterified carnitine can be measured in blood.• Oral or I.V. L-carnitine is used in carnitine deficiency or lnsufficiency in
doses of 25-100mg/kgm/day or higher.
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ORGANIC ACIDEMIA
Disorder
• Methyl malonic Acidemia.
• Propionic Acidemia.
• Multiple carboxylase deficiency.
• Ketothiolase deficiency .
Enzyme
• Methyl malonyl COA mutase.
• Propionyl COA Carboxylase.
• Malfunction of all carboxylase.
• 2 methylacetyl COA thiolase def.
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ORGANIC ACIDEMIA
Clinical Features
Vomiting, ketosis.
Thrombocytopenia , neutropenia.
Osteoporosis.
Mental retardation.
Treatment
Hydration / alkali.
Calories to catabolic state.
Exchange transfusion.
Low protein diet.
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ORGANIC ACIDEMIA
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LYSOSOMAL STORAGE DISORDERS
• Glycogen Storage Diseases
• Sphingolipidoses common in eastern jews
(Lipidoses And Mucolipidoses)
• Mucopolysaccharidoses
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Lysosomal Storage DiseaseLysosomal Storage DiseaseDiseaseDisease Enzyme Defiency Enzyme Defiency Major Accumulating Major Accumulating
MetaboliteMetabolite
GlycogenosisGlycogenosis
Type II (Pompe disease)Type II (Pompe disease) GlucosidaseGlucosidase GlycogenGlycogen
SphingolipidosesSphingolipidoses
GGM1M1 gangliosidoses gangliosidoses
GGM2 M2 gangliosidosesgangliosidoses
Tay-Sachs diseaseTay-Sachs disease Gaucher diseaseGaucher disease Niemann-Pick diseaseNiemann-Pick disease
ββ-galactosidase-galactosidase
Hexosaminidase AHexosaminidase AGlucocerebrosidasGlucocerebrosidaseeSphingomyelinaseSphingomyelinase
GGM1M1 gangliosides, gangliosides, galactose-containing galactose-containing oligosaccharidesoligosaccharides
GGM2 M2 gangliosideganglioside
GlucocerebrosideGlucocerebrosideSphingomyelinSphingomyelin
MucopolysaccharidosMucopolysaccharidoseses
MPS I H (Hurler)MPS I H (Hurler)
MPS II (Hunter)MPS II (Hunter)(X-linked recessive)(X-linked recessive)
αα--L-IduronidaseL-Iduronidase
L-Iduronosulfate L-Iduronosulfate sulfatasesulfatase
Heparan sulfateHeparan sulfateDermatan sulfateDermatan sulfate
Heparan sulfateHeparan sulfateDermatan sulfateDermatan sulfate
Glycogen Storage Diseases
Name Enzyme Symptoms Type O Glycogen synthetase Enlarged, fatty liver; hypoglycemia when fasting
von Gierke (Type IA)
Glucose-6-phosphatase Hepatomegaly; slowed growth; hypoglycema; hyperlipidemia
Type IB G-6-P translocase Same as in von Gierke's disease but may be less severe; neutropenia Pompe
(Type II) Acid maltase Enlarged liver and heart, muscle weakness
Forbe (Cori) (Type III)
Glycogen debrancher Enlarged liver or cirrhosis; low blood sugar levels; muscle damage and heart damage in some people
Andersen (Type IV)
Glycogen branching enzyme Cirrhosis in juvenile type; muscle damage and CHF
McArdle's (Type V)
Muscle glycogen phosphorylase
Muscle cramps or weakness during physical activity
Her (Type VI)
Liver glycogen phosphorlyase Enlarged liver; often no symptoms
Tarui (Type VII)
Muscle phosphofructokinase Muscle cramps during physical activity; hemolysis
Type VIII Unknown Hepatomegaly; ataxia, nystagmus Type IX Liver phosphorylase kinase Hepatomegaly; Often no symptoms Type X Cyclic 3-5 dependent kinase Hepatomegaly, muscle pain (1 patient) Type XI Unknown Hepatomegaly. Stunted growth, acidosis, Rickets
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Principle Groups of Glycogen Storage Diseases
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Von Gierke Disease
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LYSOSOMAL STORAGE DISORDERS
Lipidoses And Mucolipidoses
50Gauch. cell
In gaucher liver is enlarged but the rest of the body is very thin
In gaucher you see the cherry red spot appearance in the macula
52Sandhoff - Dense thalam
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Cerebral palsy --- scissoring of the legs
Lipid-retina
Lipid accumalation around the retinal arteries and veins
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LYSOSOMAL STORAGE DISORDERS
Mucopolysaccharidoses
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Clinical And Pathological Ultra structure Of Mucopolysaccharidoses
DiseaseDisease Clinical ManifestationClinical Manifestation Ultrastructure of Stored Ultrastructure of Stored MaterialMaterial
MPS type IMPS type I
HurlerHurler
Earliest, most severe Earliest, most severe developmental regressiondevelopmental regression
coarse facial featurescoarse facial features
HepatosplenomegalyHepatosplenomegaly
dystosis of bonedystosis of bone
cardiac involvementcardiac involvement
corneal clouding present in hurler corneal clouding present in hurler but absent in hunterbut absent in hunter
Fibrillogranular Fibrillogranular mucopolysaccharides in cells of mucopolysaccharides in cells of viscera and brainviscera and brain
MPS type IIMPS type II
HunterHunterX-linkedX-linked
Later developmental regressionLater developmental regression
coarse facial featurescoarse facial features
hepatosplenomegaly hepatosplenomegaly
dystosis of bone dystosis of bone
cardiac involvementcardiac involvement
minimal corneal cloudingminimal corneal clouding
Fibrillogranular Fibrillogranular mucopolysaccharides in cells of mucopolysaccharides in cells of viscera and brainviscera and brain
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57Hurler’s
In hurler :Nasal bridge is depressed , increase distance of philthrum , epicanthal folds, bossing of the head , thick eyebrows , upturn nostrils
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59 Mcopolysacch. Morquio
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Peroxisomes = Subcellular organelles involved in various essential anabolic or catabolic processes, biosynthesis of Plasmalogens and bile acids.
Due to dysfunction of a single or multiple peroxisomal enzymes, or to failure to form or maintain a normal number of functional peroxisomes.
PEROXISOMAL DISORDERSPEROXISOMAL DISORDERS
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Hypotonia.
Dysmorphia.
Psychomotor delay and seizures.
Hepatomegaly.
Abnormal eye findings such as retinitis pigmentosa or cataract.
Hearing impairment.
PEROXISOMAL DISORDERSPEROXISOMAL DISORDERS Clinical Manifestations:
Peroxisomal Disorders
• Zellweger Syndrome is autosomal recessive disorder.
(Cerebro-hepato-renal syndrome)
• Typical and easily recognized dysmorphic facies.
• Progressive degeneration of Brain/Liver/Kidney, with death ~6 mo after onset.
• When screening for PDs. obtain serum Very Long Chain Fatty Acids- VLCFAs
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Diagnosis:
Immunochemical studies for Peroxisomes.
V. Long Chain FA ( VLCFA ) level.
Chor. Vill. Samp. or/ amniocytes culture Plasmalogens
synthesis.
PEROXISOMAL DISORDERSPEROXISOMAL DISORDERS
Treatment:
Supportive, multidisciplinary interventions.
Diet: VLCFA, phytanic acid.
Organ transplantation.
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Peroxisomal Disorders
GROUP II : PERSOXISOMAL
ENZYME DEFECTS
GROUP I : GROUP I : BIOGENSISBIOGENSIS OF PEROXISOME OF PEROXISOME
GROUP III GROUP III :: POSITIVE PEROXISOMES BUT POSITIVE PEROXISOMES BUT MULTIPLEMULTIPLE DEFECTIVE DEFECTIVE ENZYME ENZYMEZellweger syndrome
(cerebrohepatorenal syndrome).
Neonatal adrenoleukodystrophy.
Infantile Refsum disease.
Hyperpipecolic acidemia.
Refsum disease.
X - linked Adreno-Leuko-Dystrophy.
Pseudo – Zellweger syndrome.
Hyperoxaluria….etc.
Zellweger – Like.
Pseudo – infantile Refsum disease.
Rhizomelic chondro-dysplasia
punctata
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Mitochondrial Disorders
Classically involve mutations in mitochondrial DNA
Follow a maternal pattern of inheritance
Highly variable with regard to penetrance and expressivity based on the variability in tissue distribution of abnormal mitochondria
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Mitochondrial Syndromes Presenting in Childhood to Adult
SyndromeSyndrome Most Common Most Common Clinical Clinical PresentationPresentation
Other Clinical Other Clinical FeaturesFeatures
Mt DNA Mt DNA DefectDefect
MELAS: myopathy, MELAS: myopathy, encephalopathy, encephalopathy, lactic acidosis and lactic acidosis and stroke-like episodesstroke-like episodes
Stroke-like episodes Stroke-like episodes in the first and in the first and second decade of second decade of life often associated life often associated with migraine with migraine headache, blood headache, blood lactate lactate
Deafness, Deafness, myopathy, diabetes myopathy, diabetes mellitusmellitus
mtDNA mutations at mtDNA mutations at 3243, 3271 3243, 3271 tRNA mutationstRNA mutations
MERRF: Myoclonic MERRF: Myoclonic epilepsy with ragged epilepsy with ragged red fibersred fibers
Progressive Progressive myoclonic epilepsymyoclonic epilepsy
Ataxia, myopathy Ataxia, myopathy deafness, short deafness, short staturestature
MtDNA A8344G MtDNA A8344G tRNA mutationtRNA mutation
NARP: Neurogenic NARP: Neurogenic weakness, ataxia weakness, ataxia and retinitis and retinitis pigmentosapigmentosa
Peripheral Peripheral neuropathy, neuropathy, myopathy, seizuresmyopathy, seizures
Leigh syndromeLeigh syndrome MtDNA 8993 MtDNA 8993 Complex V Complex V deficiencydeficiency
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Transient Hyperammonemia of Newborn:
Markedly high NH4 in an infant less than 24 HOL (hours of life), or first 1-2 DOL (day of life) before protein intake occurs.
Often in context of large, premature infant with symptomatic pulmonary disease.
Very sick infant.
Unknown precipitant, unknown etiology (possible slow delayed urea cycle initiation), with potential for severe sequelae (20-30% death, 30-40% abnl dev.) if not treated.
Does not recur after being treated.
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Clinical AbnormalityClinical Abnormality Abnormal Amino AcidAbnormal Amino Acid Presumptive DiagnosisPresumptive Diagnosis
Acute neonatal Acute neonatal presentation with presentation with ketoacidosisketoacidosis
Leucine, isoleucine, Leucine, isoleucine, valinevaline
Organic Acid DisordersOrganic Acid Disorders
Maple syrup urine disease Maple syrup urine disease Methylmalonic acidemia Methylmalonic acidemia
Propionic acidemiaPropionic acidemia
Isovaleric acidemiaIsovaleric acidemia
Acute neonatal Acute neonatal presentation with presentation with hyperammonemiahyperammonemia
Arginine, CitrullineArginine, Citrulline Urea cycle disordersUrea cycle disorders
Ornithine transcarbamylase Ornithine transcarbamylase deficiency Argininosuccinate deficiency Argininosuccinate synthase deficiency synthase deficiency Argininosuccinate lyase Argininosuccinate lyase deficiencydeficiency
Marfanoid, Marfanoid, strokes, ectopia strokes, ectopia lentis, lentis, mental mental retardationretardation
Homocystine & Homocystine & methioninemethionine
HomocystinuriaHomocystinuria
Severe Severe developmental developmental delaydelay
PhenylalaninePhenylalanine PhenylketonuriaPhenylketonuria
Clinical Presentation of Amino Acid Disorders
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Predominanat Predominanat Biochemical Biochemical Clinical FindingsClinical Findings
OtherOther Most Common DiagnosisMost Common Diagnosis
KetoAcidosisKetoAcidosis
LethargyLethargy
OdorOdor
Ammonia: Normal or slightly Ammonia: Normal or slightly elevated Ketones: Elevated elevated Ketones: Elevated Glucose: Normal Glucose: Normal
Maple syrup urine diseaseMaple syrup urine disease
AcidosisAcidosis
LethargyLethargy
OdorOdor
Ammonia: Elevated Ammonia: Elevated Glucose: Normal or Glucose: Normal or decreased Ketones: decreased Ketones: May be elevated May be elevated Lactate: Slightly elevatedLactate: Slightly elevated
Methylmalonic acidemia Methylmalonic acidemia Propionic acidemia Propionic acidemia Isolvaleric Isolvaleric acidemiaacidemia
Lactic AcidosisLactic Acidosis
LethargyLethargy
Acidosis: Usually present Acidosis: Usually present Ammonia: Normal or slightly Ammonia: Normal or slightly elevated elevated Ketones: May be elevated Ketones: May be elevated
Pyruvate dehydrogenase Pyruvate dehydrogenase Pyruvate carboxylase Pyruvate carboxylase deficiency Respiratory chain deficiency Respiratory chain disorderdisorder
HypoglycemiaHypoglycemia
LethargyLethargy
Ammonia: Lactate Acidosis Ammonia: Lactate Acidosis Ketones: Absent or Ketones: Absent or inappropriately lowinappropriately low
Fatty acid oxidation defectsFatty acid oxidation defects
HyperammonemHyperammonemiaia
LethargyLethargy
Acidosis: Absent Acidosis: Absent Respiratory Alkalosis Respiratory Alkalosis
Urea cycle disordersUrea cycle disorders
Metabolic Profiles Organic and Amino Acid Disorders Metabolic Profiles Organic and Amino Acid Disorders
Newborn screening is available dependent on population frequency for some
Expanded newborn screening for fatty acid defects recently offered
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CHILDREN AFTER THE NEONATAL PERIOD Clinical Manifestation
Mental retardation, Macro/Microcephaly.
Coarse facial features/dysmorphia.
Developmental regression.
Convulsion.
Myopathy / cardiomyopathy.
Recurrent emesis with coma and hepatic dysfunction.
Hypertonia / hypotonia.
Failure to thrive.
Ophthalmic – related problems : e.g. cataract, corneal
cloudiness, cherry red spot, optic atrophy.
Renal failure or renal tubular acidosis.
Management of IEM - NICU
• Stop nutrient triggering disorder e.g. protein, galactose
• Give high-energy intake
• NICU care to correct tissue perfusion, dehydration, acidosis
• Hyperammonemia Rx with Na benzoate, Na phenylbutyrate, arginine
• Dialysis
• Insulin to control hyperglycemia and reduce catabolism
• Vitamins e.g Biotin, B6, B12
• Specific therapy e.g. carnitine, glycine
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Dependent on diagnosis and severity:Dietary or vitamin therapy
Drug therapy
BMT
Avoid known environmental triggers
Surgery
MEDICALMEDICAL