Metabolic disorders are complex disorders and this presentation have collectively explained them to make it easier for the viewers

1. 1
Metabolic Disorders
Inborn Errors Of Metabolism
DR. ABDULLAH ALOMAIR
MB ChB, MRCP (Edin), FRCP (Edin.), DCH (Glas.)
Associate Professor of Pediatrics
Consultant Pediatrician
Department of Pediatrics
PRESIDENT
SAUDI PEDIATRIC ASSOCIATION

2. 2
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
Inborn Errors Of Metabolism

3.  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

6. 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

7. 7
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.

8. 8
Metabolic Disorders
From history:
Parental history :
Consanguineous parents ‫االولى‬ ‫الدرجه‬ ‫من‬ ‫اقارب‬
Previous unexplained neonatal deaths
Particular ethnic group (in certain diseases)
Features suggestive of metabolic disorder :

9. Features suggestive of metabolic disorder :
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.

10. 10
Neonatal and Post Neonatal Presentation
Neonatal presentation
Normal-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)

11. 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.

12. Newborn Screening
the 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. – MCQ ‫عنه‬ ‫اقراء‬

13. 13
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

14. 14
Urine Odor
Inborn Error of Metabolism
Sweaty feet
Gultaric Acidemia
Maple syrup
Maple Syrup urine disease
Boiled cabbage
Hypermethioninemia
Mousy or musty
Phenylketonuria
Rotten fish
Trimethylaminuria
INBORN ERRORS OF AMINO ACID METABOLISM
ASSOSIATED WITH ABNORMAL ODOR

16. They may come with flattened mid-face, indistinct philtrum, low nasal bridge and
single palmar crease.
Small chin is called
micrognathia

18. 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.

19. 19
Genetic:
Establish diagnosis.
Carrier testing.
Pedigree analysis, risk counseling.
Consideration of Prenatal diagnosis for pregnancies at
risk.
MANAGEMENT OF IEM

20. 20
 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 , FAMILIAL
MANAGEMENT OF IEM

21. 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

22. 22
‫اوال‬ : Galactosemia
Examples of some metabolic disorders :

23. 23
: Carbohydrates
Galactosemia
Enzyme 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.

24. ‫ثانيا‬ : CYSTIC FIBROSIS
exocrine disorder ‫مهمه‬
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

25. 25
AMINO ACID DISORDERS
‫ثالثا‬ : Phenyl Ketonuria (PKU)
Phenylalanine Tyrosine
Hydroxylase
Phenylalanine
Phenyl ethylamine Phenyl pyruvic acid
Phenyl pyruvic acid is what gives the urine its smell because its ketonic and acidic.

26. 26
Phenylketonuria PKU
•Remember : phenylalanine is an essential protein .
•Phenyl ethylamine + phenylpyrunivic acid give the child bad smell and it toxic to the brain
•babies with this condition present with melanin deficiency

27. 27
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
DIAGNOSIS
• Screening : Guthrie
Test.
• High Phenylalanine >
20 mg/dl.
• High Phenyl pyruvic
acid.
TREATMENT
• DIET.
• BH4 (Tetrahydrobiopterin).
• L – dopa and 5-
hydroxytryptophan.
CLINICAL FEATURES

28. 28
PKU

29. 29
‫رابعا‬ : Albinism

30. Iris had fibrous tissue, and it’s colourless and is red due to
vessels.

31. ‫خامسا‬: Congenital adrenal
hyperplasia
• Congenital adrenal hyperplasia (CAH) refers to any of
several autosomal recessive diseases resulting
from mutations of genes forenzymes mediating the
biochemical steps of production
of cortisol from cholesterol by the adrenal
glands (steroidogenesis).[1]
• Most of these conditions involve excessive or deficient
production of sex steroids and can alter development
of primary or secondary sex characteristics in some
affected infants, children, or adults.
• Etiology : 21-hydroxylase deficiency MCQ
31

32. cont
• Screening :
• Currently, in the United States and over 40
other countries, every child born is
screened for CAH at birth. This test will
detect elevated levels of 17-hydroxy-
progesterone (17-OHP). Detecting high
levels of 17-OHP enables early detection
of CAH. Newborns detected early enough
can be placed on medication and live a
relatively normal life. 32

33. cont
• Treatment of all forms of CAH may include any of:
• supplying enough glucocorticoid to reduce hyperplasia
and overproduction of androgens or mineralocorticoids
• providing replacement mineralocorticoid and extra salt if
the person is deficient
• providing replacement testosterone or estrogen at
puberty if the person is deficient
• additional treatments to optimize growth by delaying
puberty or delaying bone maturation
33

34. 34
‫سادسا‬ : 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. Pt will have Lens abnormalities ‫مهمه‬

35. 35
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)

36. 36
Homocystinuria

37. Amino acid disorders :
‫سابعا‬ : 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

38. 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)

39. 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

40. Important IEM Treatment supplements:
• Carnitine for elimination of Organic Acid through
creation of carnitine esters.
• Sodium Benzoate, phenylacetate and
phenylbutyrate for Hyperammonemia
elimination.

41. ‫ثامنا‬: CARNITINE
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.

42. 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.
42

43. 43
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.

44. 44
ORGANIC ACIDEMIA
Clinical Features
 Vomiting, ketosis.
 Thrombocytopenia ,
neutropenia.
 Osteoporosis.
 Mental retardation.
Treatment
 Hydration / alkali.
 Calories to  catabolic
state.
 Exchange transfusion.
 Low protein diet.

45. 45
ORGANIC ACIDEMIA

46. 46
‫تاسعا‬ : LYSOSOMAL STORAGE
DISORDERS
• 1- Glycogen Storage Diseases
• 2- Sphingolipidoses common in
eastern jews
(Lipidoses And Mucolipidoses) 
common in Ashkenazi Jews ‫مهمه‬
Pt present with cherry red spot in
the eye + atrophic dick
• 3- Mucopolysaccharidoses

47. 47
Lysosomal Storage Disease
Disease Enzyme Defiency Major Accumulating
Metabolite
Glycogenosis
Type II (Pompe disease) Glucosidase Glycogen
Sphingolipidoses
GM1 gangliosidoses
GM2 gangliosidoses
Tay-Sachs disease
Gaucher disease
Niemann-Pick disease
β-galactosidase
Hexosaminidase A
Glucocerebrosidase
Sphingomyelinase
GM1 gangliosides,
galactose-containing
oligosaccharides
GM2 ganglioside
Glucocerebroside
Sphingomyelin
Mucopolysaccharidoses
MPS I H (Hurler)
MPS II (Hunter)
(X-linked recessive)
α-L-Iduronidase
L-Iduronosulfate
sulfatase
Heparan sulfate
Dermatan sulfate
Heparan sulfate
Dermatan sulfate

48. Glycogen Storage Diseases

49. 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

50. 50
Principle Groups of
Glycogen Storage Diseases

51. 51
Von Gierke Disease

52. 52
LYSOSOMAL STORAGE
DISORDERS
Lipidoses And Mucolipidoses

53. 53
Gauch. cell
In gaucher liver is enlarged but the rest
of the body is very thin

54. In gaucher you see the cherry red
spot appearance in the macula

55. 55
Sandhoff - Dense thalam

56. 56
Cerebral palsy -
-- scissoring of
the legs
Lipid-retina
Lipid accumalation around the
retinal arteries and veins

57. 57
LYSOSOMAL STORAGE DISORDERS
Mucopolysaccharidoses

58. 58
Clinical And Pathological Ultra
structure Of Mucopolysaccharidoses
Disease Clinical Manifestation Ultrastructure of Stored
Material
MPS type I
Hurler
Earliest, most severe developmental
regression
coarse facial features
Hepatosplenomegaly
dystosis of bone
cardiac involvement
corneal clouding present in hurler but
absent in hunter
Fibrillogranular mucopolysaccharides
in cells of viscera and brain
MPS type II
Hunter
X-linked
Later developmental regression
coarse facial features
hepatosplenomegaly
dystosis of bone
cardiac involvement
minimal corneal clouding
Fibrillogranular mucopolysaccharides
in cells of viscera and brain

59. 59
Hurler’s

60. 60
Hurler’s
In hurler :
Nasal bridge is depressed , increase distance of philthrum ,
epicanthal folds, bossing of the head , thick eyebrows , upturn
nostrils ‫مهمه‬

61. 61

62. 62
Mcopolysacch. Morquio
‫شرحها‬ ‫تم‬ ‫شريحه‬ ‫اخر‬

63. 63
 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 DISORDERS

64. 64
 Hypotonia.
 Dysmorphia.
 Psychomotor delay and seizures.
 Hepatomegaly.
 Abnormal eye findings such as retinitis pigmentosa
or cataract.
 Hearing impairment.
PEROXISOMAL DISORDERS
Clinical Manifestations:

65. 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

66. 66
Zellweger

67. 67
Diagnosis:
 Immunochemical studies for Peroxisomes.
  V. Long Chain FA ( VLCFA ) level.
 Chor. Vill. Samp. or/ amniocytes culture   Plasmalogens
synthesis.
PEROXISOMAL DISORDERS
Treatment:
 Supportive, multidisciplinary interventions.
 Diet:  VLCFA,  phytanic acid.
 Organ transplantation.

68. 68
Peroxisomal Disorders
GROUP II : PERSOXISOMAL
ENZYME DEFECTS
GROUP I : BIOGENSIS OF PEROXISOME
GROUP III : POSITIVE PEROXISOMES BUT
MULTIPLE DEFECTIVE ENZYME
Zellweger 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

69. 69
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

70. 70
Mitochondrial Syndromes Presenting
in Childhood to Adult
Syndrome Most Common
Clinical
Presentation
Other Clinical
Features
Mt DNA Defect
MELAS: myopathy,
encephalopathy, lactic
acidosis and stroke-like
episodes
Stroke-like episodes in
the first and second
decade of life often
associated with
migraine headache,
blood lactate
Deafness, myopathy,
diabetes mellitus
mtDNA mutations at
3243, 3271
tRNA mutations
MERRF: Myoclonic
epilepsy with ragged
red fibers
Progressive myoclonic
epilepsy
Ataxia, myopathy
deafness, short stature
MtDNA A8344G
tRNA mutation
NARP: Neurogenic
weakness, ataxia and
retinitis pigmentosa
Peripheral neuropathy,
myopathy, seizures
Leigh syndrome MtDNA 8993
Complex V deficiency

71. 71

72. 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.

73. 73
Clinical Abnormality Abnormal Amino Acid Presumptive Diagnosis
Acute neonatal
presentation with
ketoacidosis
Leucine, isoleucine,
valine
Organic Acid Disorders
Maple syrup urine disease
Methylmalonic acidemia
Propionic acidemia
Isovaleric acidemia
Acute neonatal
presentation with
hyperammonemia
Arginine, Citrulline Urea cycle disorders
Ornithine transcarbamylase deficiency
Argininosuccinate synthase deficiency
Argininosuccinate lyase deficiency
Marfanoid, strokes,
ectopia lentis,
mental retardation
Homocystine &
methionine
Homocystinuria
Severe
developmental delay
Phenylalanine Phenylketonuria
Clinical Presentation of Amino Acid Disorders

74. 74
Predominanat
Biochemical
Clinical Findings
Other Most Common Diagnosis
KetoAcidosis
Lethargy
Odor
Ammonia: Normal or slightly
elevated Ketones: Elevated
Glucose: Normal
Maple syrup urine disease
Acidosis
Lethargy
Odor
Ammonia: Elevated
Glucose: Normal or decreased
Ketones: May be elevated
Lactate: Slightly elevated
Methylmalonic acidemia
Propionic acidemia
Isolvaleric acidemia
Lactic Acidosis
Lethargy
Acidosis: Usually present
Ammonia: Normal or slightly
elevated
Ketones: May be elevated
Pyruvate dehydrogenase
Pyruvate carboxylase deficiency
Respiratory chain disorder
Hypoglycemia
Lethargy
Ammonia: Lactate Acidosis
Ketones: Absent or inappropriately
low
Fatty acid oxidation defects
Hyperammonemia
Lethargy
Acidosis: Absent
Respiratory Alkalosis
Urea cycle 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

75. 75
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.

76. Clinical Symptomatology of Inborn Errors of Metabolism (IEM) in the
Neonate or Infant
Symptoms indicating possibility of an IEM (one or all)
Infant becomes acutely ill after period of normal behavior and feeding;
this may occur within hours or weeks
Neonate or infant with seizures and/or hypotonia, especially if seizures
are intractable
Neonate or infant with an unusual odor
Symptoms indicating strong possibility of an IEM, particularly when coupled
with the above symptoms
Persistent or r ecurrent vomiting
Failure to thrive (failure to gain weight or weight loss)
Apnea or respiratory distress (tachypnea)
Jaundice or hepatomegaly
Lethargy
Coma (particularly intermittent)
Unexplained hemorrhage
Family history of neonatal deaths, or of simila r illness, especially in
siblings
Parental consanguinity
Sepsis (particularly Escherichia coli)

77. Laboratory Assessment of Neonates
Suspected of Having an
Inborn Error of Metabolism
Routine Studies Special Studies
Blood lactate and
pyruvate
Complete blood count
and differential Plasma amino acids
Plasma ammonia Plasma carnitine
Plasma glucose Urine amino acids
Plasma electrolytes and
blood pH Urine organic acids
Urine ketones
Urine-reducing
substances

78. Inborn Errors of Metabolism of Acute Onset: Nonacidotic,
Nonhyperammonemic Features
Neurologic Features Predominant (Seizures, Hypotonia, Optic
Abnormality)
Glycine encephalopathy (nonketotic hyperglycinemia)
Pyridoxine -responsive seizures
Sulfite oxidase/santhine oxidase deficiency
Peroxisomal disorders (Zellweger syndrome, neonatal adrenoleuko -
dystrophy, infantile refsum disease)
Jaundice Prominent
Galactosemia
Hereditary fructose intolerance
Menkes kinky hair syndrome
a1-antitrypsin deficiency
Hypoglycemia (Nonketotic) : Fatty acid oxidation defects (MCAD, LCAD,
carnitine palmityl transferase, infantile form)
Cardiomegaly
Glycogen storage disease (type II phosphorylase kinase b deficiency 18
)
Fatty acid oxidation def ects (LCAD)
Hepatomegaly (Fatty): Fatty acid oxidation defects (MCAD, LCAD)
Skeletal Muscle Weakness : Fatty acid oxidation defects (LCAD, SCAD,
multiple acyl -CoA dehydrogenase

79. 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

80. 80
Dependent on diagnosis and severity:
Dietary or vitamin therapy
Drug therapy
BMT
Avoid known environmental triggers
Surgery
MEDICAL