1. Dr. Raj Kumar
Consultant Pediatrician
Rajasthan Hospital

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

9.  Hypoglycemia ?
 Hyperammonemia ?
 Convulsions?
 Stroke ?
 Encephalitis/ Meningitis ?

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

17.  Liver diseases
 Urea cycle disorders
 Fatty acid oxidation disorders
 Organic acidemia

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

21.  Fatty Acid Oxidation Disorder, CPT-I deficiency

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

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.