Dr. Raj KumarConsultant Pediatrician Rajasthan Hospital
3 year old boy Referred for recurrent loss of consciousness
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!
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
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
On admission: Unarousable, Febrile ; T =101F No bruises, petechae, No jaundice No edema feet No lymphnodes were palpable
Gr III coma Moved limbs on deep painful stimuli Hypotonia + Pupils equal and reacting to light No neck rigidity Planters: extensor
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
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
Urinary screen for metabolic disorders (urine MRST ) – normal Blood MRST- normal TLC for amino acids- normal TLC sugar- normal Tests for Galactosemia- negative
Recurrent,sudden loss of consciousness and hypoglycemia and severe hyperammonemia suggested neurometabolic syndrome more than anything else.
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
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
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.
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
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
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.
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.