Inborn Errors of Metabolism

Question 1

Inborn Errors of Metabolism

Answer 1

Inborn Errors of Metabolism ??
A genetic deficiency of enzyme
leading to the disturbance of normal metabolism leading to : Impaired formation of a normal product (that produced by
the deficient enzyme)
Accumulation of a toxic substrate (compound acted upon by an
enzyme in a chemical reaction)

IEM are rare genetic (inherited) disorders due to
defects of single genes that code for enzymes
that facilitate conversion of various substances into others products.

Question 2

.Signs and Symptoms of Metabolic Disease

Answer 2

1- Healthy at birth . Usually Well Baby with APGARs 9/9 after feeds start
2- Nonspecific problems : decreased feeding, vomiting. lethargy,
These symptoms progresses to Other symptoms and signs : • Vomiting, Diarrhea, •Failure to thrive (weight below the 5th centile )
•Hypotonia, Seizures, Encephalopathy,
•Hepatomegally, jaundice, hepatic dysfunction. •occasionally abnormal odor of urine.

Answer 3

4- Metabolic disturbance mostly Acidosis

Question 4

neonatal crises (crash) ’’sudden deterioration’’

Answer 4

Differential Diagnosis of (newborn crises)
Amino acid abnormality (MSUD), Urea cycle abnormality,Organic aciduria (proprionic, methylmalonic), Congenital lactic acidosis, Mitochondrial disorder
Asphyxia sepsis, congenital heart disease, Adrenal insufficiency,

Question 5

PKU (Phenylketonuria)

Answer 5

PKU (Phenylketonuria)
Error of amino acids metabolism (phenylalanine ) Normally phenylalanine Converted to Tyrosine by
phenylalanine hydroxylase Defect in this Enzyme leads to So phenylalanine is then partly converted into
phenylpyruvate, phenyllacetate,
These are excreted through urine, mousy in odour.

Question 6

PKU (Phenylketonuria)

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Answer 6

Screening and treatment:
Neonatal screening program : The baby’s heel is pricked
and a few drops of blood are taken. The blood is sent to the state laboratory to find out if it has more than a normal amount of phenylalanine. The purpose of these detection programs is to treat the babies before they start exhibiting symptoms of the disease. First newborn screening test was developed in 1959
Treatment: phenylalaine restricted diet

Question 7

PKU (Phenylketonuria)

Type 1 : No acute clinical symptoms

Answer 7

PKU (Phenylketonuria)
(Type 1 :   No acute clinical symptoms)
( mousy odour.)
skin and hair  disorders,
cataracts, Tremors and movement disorders Seizure Untreated leads to mental retardation, psychological disorders,

Question 8

Galactosemia

Answer 8

an inherited disorder
lack of the enzyme (galactose-1-phosphate uridyl transferase) which helps the body break down the galactose to glucose-1-phosphate
galactose – builds up and becomes toxic.

Question 9

.Galactosaemia

Classical Galactosaemia:

Answer 9

.Galactosaemia
Classical Galactosaemia:
Full term delivery Milk feeds established
1 week old:
 poor feeding, Vomiting and diarrhea.  failing to thrive and stunted physical growth Prolonged jaundice  Hepatomegally, Deranged clotting Cataracts. Renal damage CNS+Stunted Mental growth

Question 10

.How do you recognize a metabolic disorder

Answer 10

Physical examination •Skin – jaundice (prolonged) •ODOUR •Cataracts, retinitis pigmentosa
METABOLIC ACIDOSIS ANION GAP • Respiratory alkalosis • Hypoglycemia
– especially with hepatomegaly • Low BUN relative to creatinine

Question 11

Three Types

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Answer 11

Three Types
Type 1: Silent Disorders
Do not manifest life-threatening crises , Untreated could lead to brain damage and developmental disabilities Example: PKU (Phenylketonuria)
Type 2: Acute Metabolic Crises
Life threatening in infancy Children are protected in utero by maternal circulation which provide missing product or remove toxic substance Example OTC (Urea Cycle Disorders)
Type 3: Progressive Neurological Deterioration
Examples: Tay Sachs disease, Gaucher disease, Metachromatic, leukodystrophy •DNA analysis show: mutations