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Metaboloc Diseases

Infants with metabolic disorders are usually normal at birth


Symptomatology is nonspecific. Signs and symptoms may develop as early as a few hours after birth. It need high index of suspicion in Neonate:

  1. Poor feeding
  2. Lethargy
  3. Persisting vomiting
  4. Seizure
  5. Hypotonia
  6. Apnoea
  7. Respiratory distress
  8. Tachypnea & tachycardia

A history of clinical deterioration in a previously normal neonate should suggest an inborn error of metabolism.

An inborn error of metabolism should be considered in any child with one or more of the following manifestations.

  1. Unexplanied mental retardation, development delay
  2. Unexplanied convulsions
  3. Unusual odor particularly during acute illness
  4. Intermittent episodes of unexplained vomiting, acidosis or coma
  5. Hepatomegaly, Renal stones

Early onset disorder

Disorder presenting later on in childhood

• Silent disorders

• Disorder presenting with:

»Acute metabolic encephalopathy

»Metabolic acidosis


• Lysosomal storage disorder

• Tay-Sachs disorder

• Gaucher disease

• Matachromatic leukodystrophy



Classification of inherited neurometabolic disorder

Clinical features

Acute encephalopathy

Chronic (Progressive encephalopathy)

Age at presentation


Initial central nervous system symptoms





Clinical course

Neonatal or early infancy


Gray matter

Cognitive impairment

Seizures Vision impairment




Intoxication Vomiting

Lethargy or coma

Abnormal respiration

Late infancy, childhood, or adolescence


White matter


Ataxia Hyperreflexia




Energy deficiency or intoxication

Liver dysfunction Cardiomyopathy Weakness


Clinical pointers to neurometabolic disorder


Approach to a metabolic disorder in a neonate


If a neonate present with

  1. Poor feeding                    
  2. Lethargy
  3. Persistent vomiting                          
  4. Intractable seizures.                 
  5. unusual body

Than rule out

  1. Sepsis
  2. Hypoglycemia
  3. Hypoxic encephalopathy                     


Inborn Error of Metabolism

Urine Odor

Glutaric acidemia (type II)

Sweaty feet, acrid


Swimming pool

Isovaleric acidemia

Sweaty feet, acrid

Maple syrup urine disease

Maple syrup


Boiled cabbage

Multiple carboxylase deficiency

Tomcat urine

Oasthouse urine disease



Mousy or musty


Rotting fish


Boiled cabbage, rancid butter

Laboratory investigation


First line investigations (metabolic screen)



1. Cmplete blood count: (neutropenia and thrombocytopenia seen in propionic and methylmalonic academia)

2. Liver function tests

3. Kidney function test

4. Blood glucose

5. Electrolytes

6. Uric acid

7. Plasma ammonia (Normal values in newborn: 90-150 mg/dl or 64-107 mmol/L)

8. Arterial blood lactate (Normal values: 0.5-1.6 mmol/L)

9. Arterial blood gases

1. PH

2. Color

3. Odour

4. Specific gravity

5. Ketones

7. Reducing substances

Second line investigations (ancillary and confirmatory tests)

  1. Tandem mass spectrometry (TMS):
    For diagnosis of organic acidemias, urea cycle defects, aminoacidopathies and fatty acid oxidation defects
  2. Gas chromatography mass spectrometry (GCMS) of urine- for diagnosis of organic acidemias
  3. High performance liquid chromatography (HPLC):
    For quantitative analysis of amino acids in blood and urine
    Required for diagnosis of organic acidemias and aminoacidopathies
  4. Lactate/pyruvate ratio- in cases with elevated lactate (Normal 10:1 to 20:1)
  5. Urinary orotic acid- classification of urea cycle defect
  6. Enzyme assay: Available enzyme assays :
    Biotinidase assay- in cases with suspected biotinidase deficiency (intractable seizures,   seborrheic rash, alopecia)
    GALT (galactose 1-phosphate uridyltransferase) galactosemia (hypoglycemia, cataracts, reducing sugars in urine)
Urine Metabolic Screen

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