Dr Varsha V S, Praveena N Bhaskaran, Dr Jayasree C, Dr Lakshmi S Nair, Dr Perraju Bendapudi, Dr Ashwin S Prabhu, Dr Smrithi Madhava Menon(AimsNeo )DR C Jayakumar
AIMS Kochi.
Term/AGA/Male ba born normally to a 22 years old G3P1A1 mother with 3rd degree consanguinity. Mother had no medical illness.
On day 1 of life ba is noted to have hypoglycemia with poor activity and fever spikes. Examination: Vitals were stable.
Auxology: Weight: 2.85kg(>25th centile), HC: 34cm(>50th centile), Length: 47cm
Systemic examination done was normal.
Septic screen was sent and antibiotics were started for presumed sepsis.
During NICU stay ba had recurrent episodes of hypoglycemia even after starting total parentral nutrtion. Differentials considered were:
1. Sepsis
2. Inborn error of metabolism
3. Congenital hyperinsulinism
4. Congenital adrenal hyperplasia
5. Congenital hypothyroidism
Investigations: CBC: TC: 6.01K/uL/ N/L: 54%/ 35%, Hb: 15.1g/dl, Platelet count: 3.04Lac. CRP: .48mg/L, RFT/ TFT/ Serum electrolytes: normal. LFT : SGOT/PT: 78IU/L, 49IU/L,
Blood C/S: Sterile.
Newborn basic metabolic screening was normal.
So considering the h/o consanguineous marriage, TMS and GCMS dine was reported as positive for VLCAD deficiency(very long chain acyl coA dehydrogenase deficiency).
USG abdomen, Neurosonogram, Echo were normal.
Ba remained stable did not have further episodes of Ba was started on sagar formula (low fat sugar free) alternating with direct breast feeding and multivitamin supplements. Satisfactory weight gain was noted and mother was taught GRBS monitoring.
Parents were screened and showed positive for heterozygous variant of uncertain significance in ACADVLgene (acyl coA dehydrogenase, very long chain). Ba was discharged and is kept on follow up.
Discussion:
Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) is the second most common disorder of inborn error of fatty acid metabolism.
Incidence: 1:30,000 and 1:40,000 live births.
Inheritance: Autosomal recessive.
It is caused pathogenic variants in the ACADVL gene resulting in deficient enzyme in the mitochondrial beta oxidation of long chain fatty acids (chain length of 14-20 carbons). Thus leads to decreased energy production leading to hypoglycemia.
Clinical features: It can present heterogeneously
1. Severe Infantile VLCADD: Has an early onset, within first month of life. It has high mortality and high incidence of hypoketotic hypoglycemia, hepatomegaly, cardiac arrythmias, cardiomyopathy and pericardial effusion.
2. Moderate VLCADD: Later onset and usually presents with lower mortality, hypoketotic hypoglycemia, hepatomegaly, cardiac arrythmias and rarely cardiomyopathy.
3. Mild or late onset VLCADD: Presents in older children and young adults with isolated triggered exercise, fasting or stress . In rare cases it can lead to renal failure and can be fatal.
Management: Nutritional intervention is the corner stone of treatment. The goals of nutrition management is to minimize the production of abnormal fatty acid metabolites. Nutrition therapy is tailored individually, dependent on the severity of the disorder and patient’s age and typically includes restriction of dietary intake of long chain triglycerides together with medium chain triglycerides.
Prognosis: Is much less certain. Infants usually presents with cardiomyopathy and can present with sudden death.
Complications : Cardiomyopathy, hypotonia, hypoketotic hypoglycemia, and rhabdomyolysis.