Is there any relationship between mutation in CPS1 Gene and pregnancy loss?|
Talebi, Mehrdad; Mehrjardi, Mohammad Yahya Vahidi; Kalhor, Kambiz & Dehghani, Mohammadreza
Background: Carbamoyl phosphate synthetase 1 (CPS1) is a liver-specific enzyme with
the lowest enzymatic rate, which determines the overall rate of the other reactions in
the pathway that converts ammonia to carbamoyl phosphate in the first step of the urea
cycle. Carbamoyl phosphate synthetase 1 deficiency (CPS1D), which usually presents
as lethal hyperammonemia, is a rare autosomal recessive hereditary disease.
Case: We report a case of a two-day-old female neonate with lethal hyperammonemia.
The newborn infant was presented with hyperammonemia (34.7 𝜇g/ml; reference
range 1.1–1.9). In Plasma amino acid analysis, there was a significant elevated levels of
alanine (3,004 𝜇mol/L; reference range, 236–410 𝜇mol/L), glutamine (2,256 𝜇mol/L;
reference range, 20–107 𝜇mol/L), asparagine (126 𝜇mol/L; reference range, 30–69
𝜇mol/L), glutamic acid (356 𝜇mol/L; reference range, 14–192 𝜇mol/L), aspartic acid
(123 𝜇mol/L; reference range, 0–24 𝜇mol/L), and lysine (342 𝜇mol/L; reference range,
114–269 𝜇mol/L). We cannot diagnose the urea cycle disorder (UCD) CPS1D properly
only based on the quantity of biochemical intermediary metabolites to exclude other
UCDs with similar symptoms. Following next generation sequencing determined one
homozygous mutation in CPS1 gene and also this mutation was determined in her
parents. The identified mutation was c.2758G > C; p.Asp920His, in the 23 exon of
CPS1. This novel homozygous mutation had not been reported previously.
Conclusion: We applied whole exome sequencing successfully to diagnose the patient
with CPS1D in a clinical setting. This result supports the clinical applicability of whole
exome sequencing for cost-effective molecular diagnosis of UCDs.
CPS1 deficiency; Hyperammonemia; Urea cycle disorder; Whole exome sequencing.