Dr. Raj Kumar

Consultant Pediatrician

Rajasthan Hospital

A case of recurrent loss of consciousness

3 year old boyReferred for recurrent loss of consciousness

Case details

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!

The history

Non-consanguineous familyNormal birth details and early developmentFamily history of death in a male sibling

at 2 days of age- unexplainedIn between episodes normal examination

Background

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

Previous admissions

On admission:Unarousable, Febrile ; T =101FNo bruises, petechae, No jaundiceNo edema feetNo lymphnodes were palpable

At our institute

Gr III comaMoved limbs on deep painful stimuliHypotonia +Pupils equal and reacting to lightNo neck rigidityPlanters: extensor

CNS

No distentionNo visible veinsNo umbilical herniaLiver enlargement of 3 cms, soft with sharp

edgesSpleen not palpableNo ascites

Other systems were found to be normal

Abdomen

Hypoglycemia ?Hyperammonemia ?Convulsions?Stroke ?Encephalitis/ Meningitis ?

Differential diagnoses?

What should we do now?

On admission low blood sugar of 32, Ammonia of 500, Lactate 2.3, normal pH and base excess of -

6.5CBC: Normochromic normocytic anemia,

WBC 12,000 with 60% neutrophils, peripheral smear unremarkable

Urea 28, Creatinine 0.8, Na 139, K 4.0Liver function tests- ALT 123, Bil 1.2, PT

16/14 LDH 996, Alb 4.2

Investigations

Urinary screen for metabolic disorders (urine MRST ) – normal

Blood MRST- normalTLC for amino acids- normalTLC sugar- normalTests for Galactosemia- negative

Investigations

Biotinidase- negativeG6PD- normal levelsUrinary orotic acid- normalPlasma amino acidsHPLC- normalHPLC nucleic acid- normalPlasma amino acids LC/MS- normal patternGC-MS Organic acids- Elevated 2-

oxoglutaric acid

Recurrent, sudden loss of consciousness and hypoglycemia and severe hyperammonemia suggested neurometabolic syndrome more than anything else.

Our thought process.....

If you have a patient with :Neonatal progressive or recurrent

encephalopathyEpilepsy that is refractory to treatment,

myoclonic epilepsyExtrapyramidal movement disordersPtosis, miosis and oculogyric crisisDisturbances of autonomic functions

When to suspect neurometabolic syndrome?

AmmoniaAA including homocysteineOA in urinePurines and pyrimidines in urine and bed side

sulphite testProlactin in serumWhole blood serotonineMetabolic tests in CSFMRS of brainNMR (Nuclear Magnetic Resonance) of CSF

Investigations in neurometabolic syndrome

Liver diseasesUrea cycle disordersFatty acid oxidation disordersOrganic acidemia

Hyperammonemia

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.

Any clue ?

High free fatty acids, and low beta-hydroxy butyrate

High total carnitineCK and Uric acidGrossly elevated C0/C16-18 ratio suggestive

of CPT-1 deficiency by TMSHigh Dicarboxylic aciduria suggesting omega

oxidationEnzyme studies in fibroblast and lymphocytesMolecular diagnosis

Further tests

Fatty Acid Oxidation Disorder, CPT-I deficiency

Final diagnosis

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

Treatment

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.

When to suspect Fatty Acid Oxidation Disorders ?

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)

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

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

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.

Long term management

THANK YOU ALL