Recurrent encephalopathy and hyperammonemia in new born: case of arginosuccinic aciduria

Authors

  • Parminder Singh Department of Pediatrics, 155 Base Hospital, Tezpur, Assam, India
  • Divya Gupta Department of Pathology, 155 Base Hospital, Tezpur, Assam, India

DOI:

https://doi.org/10.18203/2349-3291.ijcp20184308

Keywords:

Arginosuccinic aciduria, Genetic analysis, Hyperammonemia, Recurrent encephalopathy

Abstract

Urea cycle disorders result from defects in the metabolism of waste nitrogenous compounds derived from the breakdown of proteins and other nitrogen-containing molecules. Argininosuccinic aciduria is a rare autosomal recessive heterogeneous urea cycle disorder, which leads to the accumulation of argininosuccinic acid in the blood and urine. It is caused by defect in the argininosuccinate lyase (ASL) gene, which regulates the breakdown of argininosuccinate to fumarate and arginine in the urea cycle. They are a heterogeneous group of disorders which are associated with hyperammonemia resulting in severe neurological dysfunction like encephalopathy, seizures, developmental and psychomotor delay. The severe central nervous system dysfunction is by alteration of amino acid and neurotransmitters pathways and interference with normal cerebral energy metabolism and oxidative stress. Ammonium toxicity to the brain provokes irreversible damage due to cortical atrophy, edema, and demyelination, resulting in seizures, coma, and even death. We report such a case of urea cycle defect in a newborn that presented with recurrent encephalopathy with hyperammonemia precipitated by minor infections. Detailed investigations including genetic analysis lead to the diagnosis of argininosuccinic aciduria.

References

Çelik K, Terek D, Olukman Ö, Kağnıcı M, Gözmen ŞK, Serdaroğlu E. Urea cycle disorders in neonates: six case reports. J Pediatr Res. 2017;4(2):85.

Maestri NE, Clissold D, Brusilow SW. Neonatal onset ornithine transcarbamylase deficiency: a retrospective analysis. J Pediatr. 1999;134:268-72.

Wen W, Yin D, Huang F, Guo M, Tian T, Zhu H, et al. NGS in argininosuccinic aciduria detects a mutation (D145G) which drives alternative splicing of ASL: a case report study. BMC medical genetics. 2016 Dec;17(1):9.

Erez A, Nagamani SC, Lee B. Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond. Am J Med Genet C Semin Med Genet. 2011;157C:45-53.

Trevisson E, Salviati L, Baldoin MC, Toldo I, Casarin A, Sacconi S, et al. Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene. Hum Mutat. 2007;28:694-702.

Waisbren SE, Gropman AL. Members of the Urea Cycle Disorders Consortium (UCDC), Batshaw ML. Improving long term outcomes in urea cycle disorders-report from the urea cycle disorders consortium. J Inherit Metab Dis. 2016;39:573-84.

Karthikeyan G, Jagadeesh S, Seshadri S, Häberle J. Citrullinemia type 1: genetic diagnosis and prenatal diagnosis in subsequent pregnancy. Indian pediatrics. 2013;50(10):965-6.

Häberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Diseases. 2012;7:32.

Steiner RD, Cederbaum SD. Laboratory evaluation of urea cycle disorders. J Pediatr. 2001;13:S21-9.

Sander J, Janzen N, Sander S, Steuerwald U, Das AM, Scholl S, et al. Neonatal screening for citrullinemia. Eur J Pediatr. 2003;162:417-20.

Downloads

Published

2018-10-22