Coexistence of 21-hydroxylase deficiency and Gitelman syndrome in a neonate presenting with severe hyponatremic seizures: a case report.

INTRODUCTION

21-hydroxylase deficiency is an autosomal recessive genetic disease caused by congenital deficiency of 21-hydroxylase. Gitelman syndrome (GS) is a rare autosomal recessive renal tubular disease. The coexistence of these two diseases in the same patient is rare in clinical practice.

METHODS

We report the case of a newborn with concurrent 21-hydroxylase deficiency and GS who presented with severe hyponatremic seizures. We describe the clinical manifestations, physical examination findings, laboratory results, treatment, and follow-up.

RESULTS

A male newborn was admitted to the neonatal intensive care unit at Tianjin Children's Hospital for intermittent convulsions for 10 days. Laboratory tests showed severe hyponatremia, with a serum sodium of 88 mmol/L, which was considered the cause of the convulsions. Further testing showed markedly elevated 17-hydroxyprogesterone (17-OHP) and adrenocorticotrophic hormone (ACTH) levels (17-OHP, 740.2 ng/mL; reference range, <3 ng/mL; ACTH, 488.4 pg/mL; reference range, 7.2-63.3 pg/mL). Therefore, 21-hydroxylase deficiency was clinically diagnosed. Serum potassium was mostly within the normal range, but hypomagnesemia was recorded. Whole-exome sequencing and multiplex ligation-dependent probe amplification combined with long-range PCR were performed. There were two pathogenic variants identified, a homozygous variant of 293-13C>G (p.)? in intron 2 in the CYP21A2 gene and a compound heterozygous variant of c.473G>A (p.Arg158Gln) and c.2720 + 3A>T (p.)? in the SLC12A3 gene. Genetic testing confirmed two rare diseases in this infant: 21-hydroxylase deficiency and Gitelman syndrome.

CONCLUSION

The coexistence of 21-hydroxylase deficiency and GS in a neonate has rarely been reported. These two pathologies determine the opposite values of potassium (hyperkalemia in 21-hydroxylase deficiency and hypokalemia in GS). This case report provides diagnostic and treatment insights for clinicians and highlights the value of genetic testing when the diagnosis is uncertain.