2. 3 year old boy
Referred for recurrent loss of consciousness
3. The child would be perfectly well before these
episodes would start
Following trivial illness, he would start with
vomiting and soon loose consciousness.
Would be admitted to hospital, where he would be
given iv fluids and recover again in no time!
4. Non-consanguineous family
Normal birth details and early development
Family history of death in a male sibling at 2 days
of age- unexplained
In between episodes normal examination
5. Notes from previous admissions suggested that he was
noted to have hypoglycemia during these episodes.
Neurological examination was unremarkable except
hypotonia in one note; no neck rigidity and no focal
weakness was noted
6. On admission:
Unarousable,
Febrile ; T =101F
No bruises, petechae,
No jaundice
No edema feet
No lymphnodes were palpable
7. Gr III coma
Moved limbs on deep painful stimuli
Hypotonia +
Pupils equal and reacting to light
No neck rigidity
Planters: extensor
8. No distention
No visible veins
No umbilical hernia
Liver enlargement of 3 cms, soft with sharp edges
Spleen not palpable
No ascites
Other systems were found to be normal
11. On admission low blood sugar of 32,
Ammonia of 500,
Lactate 2.3, normal pH and base excess of -6.5
CBC: Normochromic normocytic anemia, WBC 12,000
with 60% neutrophils, peripheral smear unremarkable
Urea 28, Creatinine 0.8, Na 139, K 4.0
Liver function tests- ALT 123, Bil 1.2, PT 16/14 LDH
996, Alb 4.2
12. Urinary screen for metabolic disorders (urine MRST )
– normal
Blood MRST- normal
TLC for amino acids- normal
TLC sugar- normal
Tests for Galactosemia- negative
13. Biotinidase- negative
G6PD- normal levels
Urinary orotic acid- normal
Plasma amino acids
HPLC- normal
HPLC nucleic acid- normal
Plasma amino acids LC/MS- normal pattern
GC-MS Organic acids- Elevated 2-oxoglutaric acid
14. Recurrent,sudden loss of consciousness and
hypoglycemia and severe hyperammonemia suggested
neurometabolic syndrome more than anything else.
15. If you have a patient with :
Neonatal progressive or recurrent encephalopathy
Epilepsy that is refractory to treatment, myoclonic
epilepsy
Extrapyramidal movement disorders
Ptosis, miosis and oculogyric crisis
Disturbances of autonomic functions
16. Ammonia
AA including homocysteine
OA in urine
Purines and pyrimidines in urine and bed side sulphite
test
Prolactin in serum
Whole blood serotonine
Metabolic tests in CSF
MRS of brain
NMR (Nuclear Magnetic Resonance) of CSF
18. Urine had no ketones while the child was
hypoglycemic !!
Thus this child had hypo-ketotic hypoglycemia
This raised the possibility of FAOD; hyperammonemia
is a known finding in FAOD.
19. High free fatty acids, and low beta-hydroxy butyrate
High total carnitine
CK and Uric acid
Grossly elevated C0/C16-18 ratio suggestive of CPT-1
deficiency by TMS
High Dicarboxylic aciduria suggesting omega
oxidation
Enzyme studies in fibroblast and lymphocytes
Molecular diagnosis
22. For acute episodes he was treated with oral sodium
benzoate, IV Dextrose, IV carnitine and lactulose.
Within 3 days ammonia decreased to 100 and
subsequently 41- level of consciousness improved
23.
24. Disorders of fatty oxidation display two general types of
presentation.
First, hypoketotic hypoglycemia, and clinical picture
of Reye syndrome.
In fact, it is now clear that most patients who appear
to have Reye syndrome have an inborn error of
metabolism, the most common, being MCAD
deficiency and OTC deficiency.
25. Second, reflects the chronic disruption of muscle
function with symptoms relevant to myopathy or
cardiomyopathy, including weakness, hypotonia,
congestive heart failure, or arrhythmia.
Both types of presentations may be seen in the same
family or even in the same individual.
Another presentation is with the sudden infant death
syndrome (SIDS)
26. Episodic illness usually occurs first between 6 months
and 2 years, usually following fasting for 12 hours or
more as a consequence of intercurrent infectious
disease.
The episode may be ushered in with vomiting or
lethargy, or it may begin with a seizure. It is
progressive rapidly to coma
27. Hepatomegaly is usually present at the time of the
acute illness.
Liver biopsy at the time reveals abundant deposits of
lipid in microvesicular pattern.
This and hyperammonemia have often led to a
diagnosis of Reye syndrome
Cerebral edema and herniation have been reported in
an acute lethal episode
28. In long-term management use supplemental
cornstarch, at least for evening and night feedings.
The initial dosage we have employed is 0.5 g/kg (1 Tbsp
8 g), usually working up to 1.0 g/kg.
Some reduction in the intake of fat appears prudent,
but this does not need to be excessive.
Supplementation with carnitine is currently advised.