Dr Adeena ,Dr Sajith Kesavan, Dr Greeshma Issac,Dr Sheela Namboothiri, Dr CJayakumar
Five-month-old girl
first born to a non-consanguineous couple presented with
poor activity for 4 days followed fever, multiple episodes of vomiting, altered breathing and decreased urine output of 1 day duration. Out side hospital hypoglycemia and severe metabolic acidosis (pH 6.995, HCO3 -5.6) was noted and hence referred.H/o a brief paroxysmal event noted prior to the fever
Ba was born term weighing 2.6 kg. She was developmentally normal and immunized for age.
At admission, ba was intubated. Spo2 – 92%, BP-78/29, HR 173/min, RR -60/min.
P/a-soft with firm liver palpable 5 cm below right costal margin
ABG at admission- severe metabolic acidosis (pH-6.95, hco3-3),dyselectrolemia and hyperammonemia.
TC 32000(N39, L 57) Hb -9.9,plt 468,
CRP 1.6mg/dl
.Corrections were given and ba was initiated on peritoneal dialysis. At this point IEM- probably organic acidemia was considered
. MRI brain with spectroscopy was also suggestive of IEM. Most probably MMA/? propionic acidemia.
TMS/ GCMS, Whole exome sequencing and plasma HPLC aminoacid was sent.
She was managed for sepsis, metabolic crisis and started on mitochondrial cocktail.
Tandem mass spectroscopy showed low free carnitine and low free /acyl carnitine ratio with mildly elevated C4OH,C5DC not elevated. Plasma aminoacid levels showed elevated glycine and lysine. GCMS: increased lactic acid , ketones as seen in HMGcoA synthase deficiency but with increased glutaric acid and presence of 3 hydroxy glutaric acid which was suggestive of glutaric aciduria type 1,hence couldnot be ruled out.
Awaiting WES reports the ba was started on protein free liquid diet (kanji and glucose solutions) and later transitioned to metanutrition AAMD 1-aminoacid metabolic disorder formula that was protein free along with Carnitine and riboflavin supplementation begun.
Whole exome report revealed Fatty acid oxidation defect -HMG CoA synthase 2 defeciency (homozygous-autosomal recessive) for which no proven dietary therapy available.
Parents were counselled regarding adequate calorie intake and glucose maintenance during periods of stress or infection that otherwise could trigger a similar metabolic crisis and advise to avoid fasting.
HMG Coa synthase deficiency
A rare autosomal recessive Inborn error of metabolism that affect ketone body synthesis.
Mutation in HMGCS2 gene that produces the enzyme that catalyses reactions of acetyl CoA and acetoacetyl CoA into HMG Coa during ketone body synthesis that’s important in energy supply in fasting and carbohydrate deprivation.
Clinical features-acute episodes include vomiting encephalopathy, hepatomegaly,hypoglycemia and dicarboxylic aciduria precipitated intercurrent infection/ prolonged fasting. A typical urine profile includes dicarboxylic aciduria and specific metabolites that appear only during periods of metabolic decompensation. However these findinga overlap with thosw foiund in other IEM which makes thee diagnosis difficult. Confirmatory testing is the molecular analysis of gene.
Take home message
IEM is an important cause for vomiting and hypoglycaemia and these children need detailed metabolic work up survival and for a good quality of life