Congenital Hyperinsulinism and Maple Syrup Urine Disease a Challenging Combination

Background: Congenital hyperinsulinism (CHI) is the most
common cause of persistent hypoglycemia in infancy, characterized by unregulated insulin secretion. CHI is a challenging
disease to diagnose and manage. Moreover, complicating the
course of the disease with another metabolic disease like Maple
syrup urine disease (MSUD) adds more challenges to the already
complex management. Case: We report a term male neonate with
uneventful birth history. He developed symptomatic hypoglycemia with a blood glucose (BG) level of 1.9 mmol/l at 21 hours of
life. A critical sample at that time showed high serum insulin of 167.7 pmol/L, C-peptide [1160 pmol/L and low ketones
confirming the diagnosis of hyperinsulinism. Amino acid profile
on dried blood spot by tandem mass spectrometry part of critical
sample was done and showed high leucine and isoleucine levels
indicating the diagnosis of MSUD. MSUD is then confirmed by
HPLC which showed the presence of allo-isoleucine at
101 umol/L, and elevated levels of the three branched chain
amino acids (leucine 724 (45.00–160.00), isoleucine 240 umol/L
(28.00–95.00), and valine 390 umol/L (60.00–294.00). The
diagnosis of CHI and MSUD was afterward confirmed by
molecular genetic testing. The finding of a known pathogenic
homozygous mutation in the ABCC8 gene (c.3748COT,
p.Arg1250*) confirmed CHI diagnosis. The presence of a
homozygous mutation in the BCKDHA (c.1087, p.Arg363Trp)
confirmed the MSUD diagnosis. The baby’s case is very
challenging managing two rare autosomal recessive disorders.
Managing his hypoglycemia with high glucose rate through
intravenous fluids, frequent feeds with special MSUD formula, and
medications for hyperinsulinism (Diazoxide and octereotide).
Unfortunately his hyperinsulinism did not respond to all medical
measures and he needed to go to a near total pancreatectomy.
Through all his complicated course, he required very meticulous
monitoring of his BG and amino acid profile (3 times/week on
average) aiming to maintain the BG at 3.9 mmol and above and
levels of the three branched chain amino acids at the disease
therapeutic targets for a neonate. Conclusion: This patient is
perhaps the only known case of the occurrence of two rare life
threatening disorders. Both hypoglycemia and Leucine encephalopathy can result in death or permanent neurological damage. This
is complicated by the fact that both disorders have direct effect on
the body metabolism of glucose and branched chain amino acids
and there management in combination is very challenging