Immune Alterations in a Patient With Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome: A Case Report.

Autor:	Silvera-Ruiz SM; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Hospital de Niños de la Santísima Trinidad, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Gemperle C; Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Peano N; Fundación para el Progreso de la Medicina, Córdoba, Argentina., Olivero V; Fundación para el Progreso de la Medicina, Córdoba, Argentina., Becerra A; División de Enfermedades Metabólicas, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina., Häberle J; Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Gruppi A; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Larovere LE; Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Hospital de Niños de la Santísima Trinidad, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.; Cátedra de Clínica Pediátrica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Motrich RD; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 May 27; Vol. 13, pp. 861516. Date of Electronic Publication: 2022 May 27 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.861516
Abstrakt:	The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive inborn error of the urea cycle caused by mutations in the SLC25A15 gene. Besides the well-known metabolic complications, patients often present intercurrent infections associated with acute hyperammonemia and metabolic decompensation. However, it is currently unknown whether intercurrent infections are associated with immunological alterations besides the known metabolic imbalances. Herein, we describe the case of a 3-years-old girl affected by the HHH syndrome caused by two novel SLC25A15 gene mutations associated with immune phenotypic and functional alterations. She was admitted to the hospital with an episode of recurrent otitis, somnolence, confusion, and lethargy. Laboratory tests revealed severe hyperammonemia, elevated serum levels of liver transaminases, hemostasis alterations, hyperglutaminemia and strikingly increased orotic aciduria. Noteworthy, serum protein electrophoresis showed a reduction in the gamma globulin fraction. Direct sequencing of the SLC25A15 gene revealed two heterozygous non-conservative substitutions in the exon 5: c.649G>A (p.Gly217Arg) and c.706A>G (p.Arg236Gly). In silico analysis indicated that both mutations significantly impair protein structure and function and are consistent with the patient clinical status confirming the diagnosis of HHH syndrome. In addition, the immune analysis revealed reduced levels of serum IgG and striking phenotypic and functional alterations in the T and B cell immune compartments. Our study has identified two non-previously described mutations in the SLC25A15 gene underlying the HHH syndrome. Moreover, we are reporting for the first time functional and phenotypic immunologic alterations in this rare inborn error of metabolism that would render the patient immunocompromised and might be related to the high frequency of intercurrent infections observed in patients bearing urea cycle disorders. Our results point out the importance of a comprehensive analysis to gain further insights into the underlying pathophysiology of the disease that would allow better patient care and quality of life. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Silvera-Ruiz, Gemperle, Peano, Olivero, Becerra, Häberle, Gruppi, Larovere and Motrich.)
Databáze:	MEDLINE
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