The many presentations

(faces) of inherited
metabolic diseases
Dr. Abdulmateen Abdulrahman Shukri
Pediatrician
Univeristy of Duhok/ College of medicine
Introduction:
The cause of signs and
symptoms of
IMD?

Why diagnosis is delayed in

patients with IMD?
Inherited metabolic disease (IMD) may present at any age and the signs
and symptoms may result from:
• Accumulation of substrate that leads to a toxic effect.
• Accumulation of a minor metabolite that in excess is toxic.
• Deficiency of a product of a specific reaction.
• Secondary metabolic phenomena.
The commonest error in managing infants and children with IMD is a
delay in diagnosis, and therefore a delay in starting treatment. Failure to
recognize an IMD may occur because its clinical features are confusing
because of:
• Genetic heterogeneity.
• A presenting inter-current illness.
• similarity with other common, acquired conditions where the
differential diagnosis has not been fully explored.
A. Neurological presentations:
1- Chronic encephalopathy:
A. Grey matter .. Developmental delay, psychomotor
retardation.
B. White matter … Gross motor delay, weakness and
incoordination.
C. Encephalopathy with problems outside the CNS.
Developmental delay is a common problem, but the features that
warrant investigation for IMD include:
• Global delay affecting all areas of development.
• Progressive course with loss of developmental milestones.
• Objective evidence of neurological dysfunction (e.g. special
senses,pyramidal tract, extrapyramidal, cranial nerves).
• Severe behaviours including irritability, impulsiveness,
aggressiveness, and hyperactivity.
• Seizures (complex partial or myoclonic) originating early in life
that are resistant to usual therapy.
45-day-old boy presents with recurrent myoclonic
seizures that were not responding to multiple anti-
epileptic medications ( phenobarbital, levetiracetam,
and phenytoin). Seizures immediately respond to
pyridoxine ( vitamin B6) injection. When has been
inadvertently stopped by parents after discharge,
seizures recurred and then terminated upon on given
injection again confirming the diagnosis of
pyridoxine-dependent seizure.
6-week-old boy had multiple daily seizures that
partially responded to sodium valproate. In addition
he had marked developmental delay and features of
encephalopathy. Examination revealed severe
extensive seborrheic dermatitis on his scalp, back
and perineal region.
Biotinidase deficiency … dramatic response to biotin.
X-linked ALD … MRI white matter changes
Investigations for chronic encephalopathy
• Clinical: developmental assessment and
neurological examination
• Imaging: MRI of head; X-rays of hands, chest,
lateral spine
• Blood: plasma amino acids; ammonia; lactate
• Urine: amino acids, organic acids, and
mucopolysaccharide and oligosaccharide screen
• Electrophysiology: auditory brainstem refl exes;
visual-evoked potentials; somatosensory-evoked
potentials; nerve conduction;EMG; EEG
2- Acute encephalopathy
The likely causes are: hypoglycaemia;
hyperammonaemia; amino acidopathy; organic
aciduria ; fatty acid oxidation defect ; mitochondrial
defect.
3- stroke or stroke-like episodes.
Fabry disease
4-year-old girl with
right-sided stroke
with her 11-year-old
tall brother who
underwent lens
surgery before.
Homocystinuria
Cranial MRI … acute infarct
Coagulation screening … normal
Screening for autoimmune diseases …
negative
Metabolic … elevated homocysteine,
methionine and normal vitamin B12
Rx: Anti-coagulation, vitamin B6, later on
betaine if no response.
4- Movement disorders.
5- Myopathy.
6- Autonomic dysfunction.
7- Psychiatric disturbances.
B. Metabolic acidosis.
Either from abnormal bicarbonate loss or
accumulation of organic anion.
Anion gap, serum chloride, urine anion gap for the
first category ( GI vs renal causes).
Causes of the second category are: lactic acidosis,
ketoacidosis or organic aciduria.
C. Storage or
dysmorphism.
D. Hepatic:
These include:
1- Jaundice.
2- Hepatomegaly.
3- Hypoglycemia.
4- Hepatocellular dysfunction.
Glycogen storage disease type
IV in a 5-year-old girl with
marked abdominal distension
with hepatosplenomegaly.
E. Cardiac:
These include: cardiomyopathy, arrhythmias and
coronary artery disease.
Glycogen metabolism (hypertrophic cardiomyopathy)
Pompe disease (GSD II)—presents in early infancy
with marked skeletal myopathy, massive
cardiomegaly (large QRS, left axis deviation,
shortened PR, T-wave inversion).
Fatty acid metabolism (dilated cardiomyopathy)
Systemic carnitine defi ciency: presents with skeletal
myopathy, hypotonia encephalopathy, hepatic
syndrome (hepatomegaly, hypoglycaemia,
hepatocellular dysfunction).