By Prof. MANAL ELDEFRAWY Awareness of some IEM 2011. Management of Metabolic Emergencies. Objectives. When to suspect a metabolic disorder ? Immediate investigations Specific investigations Which emergency measures ? Diagnostic algorithm Case presentation.
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Single gene defect in an enzyme or transport protein, which results in a block in a metabolic pathway of proteins ,CHO, fats, or complex molecules.
toxic accumulations of substrates before the block, intermediates from alternative metabolic pathways, defects in energy production caused by a deficiency of products beyond the block,
or a combination of these metabolic deviations
estimated to be approximately
1 in 4000 live births
The inheritance is mostly autosomal recessive with male to female ratio of 1:1
Time & Pattern of Onset
Typically born healthy, symptom free period
Deterioration with poor feeding, vomiting, lethargy, apnea seizures, coma.
e.g. a.acidopathies, Organic acidemia, UCDs , CHO intolerance.
B) Energy deficiencies
No apparent Symptom free
Overwhelming neurologic deterioration apnea, seizures, coma
e.g. FAO defects, Mitochondrial disorders, peroxisomal disorders
Increase carnitine ester in fatty acid oxidation defect, organic academias, ketosis
NKH is diagnosed by the presence of elevated CSF to plasma glycine ratio
Decrease CSF glucose/to blood glucose…..glucose transporter defect
Plasma very long chain fatty acids (VLCFAS),
Phytanic acid, erythrocyte plasmalogen levels
Frozen whole and heparinized bl., serum, CSF & urine (store at -20°C).
Severe, persistent, without other etiology
If with metabolic acidosis e.g. OA,
GSD Type 1 , Fructose 1,6Diphosphatase deficiency, FAO (hallmark Non ketotic)
N.B :Hypoglycemia (plasma glucose level
< 50 mg/dL)
>100 mcg/dL in the neonate
> 80 mcg/dL beyond the neonatal period
is considered elevated & toxic.
This can lead to Encephalopathy and death OR
Devastating neurological sequelae.
Neurological sequelae and survival depend on the length of hyperammonemic coma(better prognosis <36h or<2days).
Normal PH or alkalosis
Organic acidemiaPyruvate metabolism
Plasma aminoacids Urea cycle disorders
Fatty acid oxidation (FAO)
Urine Orotic acid
period of hyperirritability and profuse vomiting
then gradual and progressive lapse in the level of consciousness which worsen upon the introduction of depakene to control the seizure .
Past history : revealed two similar episodes of disturbed conscious level :
-The first was at 7days in neonatal period .
CT at that time revealed brain edema.
-The second episode was at the age of 18 months.
revealed a semi conscious child with generalized axial and limb hypotonia,
Fair complexion , apathy , GDD (motor &mental) . Normal abd. Exam. Pt . weighted 6 kg , H.C. 42 cm , length 69 cm (all< 3rd percentile for age)
HGB : 10.5 , normocytic,normochromic a.
ABG: metabolic alkalosis ( repeatedly)
Ammonia : high ( repeatedly) > 300ug/dl TMS: ( HHH syndrome)
Hyperornithinemia and Homocitrullinemia
Date : 9/2010
- 2 years old male
-3mths ago he developed recurrent attacks of G.E. & M.A.
-Then he suffered from coma for nearly a week ?.
-After that he developed severe failure to thrive.
Expanded metabolic screen using LC-MS/MS showed
T2w Brain MRI showing widening of extraaxial CSF spaces, and sylvian fissure, picture of severe brain atrophy
TW1 Brain MRI showing frontotemporal atrophy
The condition started at the age of 5 days by
Jaundice which was diagnosed as physiological , no treatment .
For the following 3 month the mother noticed gradual abd . distention and no improvement in colour .
the baby was lethargic with tachypnea , hepatomegaly (span 10cm ) and cholestatic jaundice ( T=9.6 , d=5.2).
He was ventilated but it was difficult
to be weaned from vent. as he developed cardiac problems as severe bradycardia and arrest.
The baby was treated with Na benzoate and glutathione analogs, vit C and vit E.He started to gain consciousness and he was weaned from the vent. The jaundice and hepatomegaly decreases .
lethargy, hypotonia, jaundice.
Hypoglycemia, elevated liver enzymes
Product ion scans of derivatized SA (top) and 5,7- dioxooctanoic acid (internal standard; bottom) and fragmentation of SA-hydrazone (inset).
A simple method for quantifying SA in dried blood spots hasbeen described by Allard et al.,2004 .
Inclusion of SA in our existing screening program couldbe achieved with little additional manual work.
Patients with > 250 µg copper per gram of dry liver tissue are considered to have Wilson's disease.
Das SK and Ray K (2006) Wilson's disease: an update
Nat ClinPractNeurol2: 482–493