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Volume 16
Issue 9
10.3390/genes16091009
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Case Report

Variants in GSTZ1 Gene Underlying Maleylacetoacetate Isomerase Deficiency: Characterization of Two New Individuals and Literature Review

by
Ferdinando Barretta
1,†,
Fabiana Uomo
1,2,†,
Alessandra Verde
3,
Mariagrazia Fisco
1,
Giovanna Gallo
1,
Lucia Albano
1,
Daniela Crisci
1,
Cristina Mazzaccara
1,4,
Pietro Strisciuglio
3,
Margherita Ruoppolo
1,4,
Simona Fecarotta
5,
Giancarlo Parenti
3,
Giulia Frisso
1,4,* and
Alessandro Rossi
3
1
CEINGE Biotecnologie Avanzate–Franco Salvatore s.c.ar.l., 80131 Naples, Italy
2
Department of Advanced Biomedical Science, University of Naples “Federico II”, 80131 Naples, Italy
3
Department of Translational Medical Science, Section of Paediatrics, University of Naples “Federico II”, 80131 Naples, Italy
4
Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, 80131 Naples, Italy
5
Department of Integrated Maternal-Fetal Care, “Federico II” University Hospital, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to the work.
Genes 2025, 16(9), 1009; https://doi.org/10.3390/genes16091009
Submission received: 21 July 2025 / Revised: 7 August 2025 / Accepted: 19 August 2025 / Published: 26 August 2025
(This article belongs to the Special Issue Genetics and Genomics of Heritable Pediatric Disorders)
Review Reports Versions Notes

Abstract

Introduction: Elevated succinylacetone (SA) is the hallmark of tyrosinemia type 1, which requires immediate treatment. Mild SA elevation has also been recently reported in maleylacetoacetate isomerase deficiency (MAAID). Methods: We report on two cases of MAAID, review clinical features of MAAID and discuss its management. Results: Both cases displayed elevated SA and normal Tyrosine levels at newborn screening. Case 1 showed intermittent SA elevation; Nitisinone and dietary treatment were started, then discontinued after the identification of two variants in the GSTZ1 gene and the definitive diagnosis of MAAID. Case 2, showing no SA elevation at the confirmatory tests and two variants in the GSTZ1 gene, did not start treatment. mRNA analysis confirmed the pathogenicity of the c.68-12 G>A variant, found in both patients. Discussion: MAAID should be considered in newborns showing elevated SA and no variants in the FAH gene. Our study reports for the first time the course of SA in a patient affected by MAAID. Furthermore, it expands the molecular epidemiology of this rare disease, also investigating the pathogenicity of a novel splicing mutation. Although our data argue against medical treatment in MAAID, longer follow-up data are warranted.
Keywords: tyrosinemia type 1; newborn screening; succinylacetone; maleylacetoacetate isomerase deficiency; GSTZ1 mutations; mRNA analysis tyrosinemia type 1; newborn screening; succinylacetone; maleylacetoacetate isomerase deficiency; GSTZ1 mutations; mRNA analysis

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MDPI and ACS Style

Barretta, F.; Uomo, F.; Verde, A.; Fisco, M.; Gallo, G.; Albano, L.; Crisci, D.; Mazzaccara, C.; Strisciuglio, P.; Ruoppolo, M.; et al. Variants in GSTZ1 Gene Underlying Maleylacetoacetate Isomerase Deficiency: Characterization of Two New Individuals and Literature Review. Genes 2025, 16, 1009. https://doi.org/10.3390/genes16091009

AMA Style

Barretta F, Uomo F, Verde A, Fisco M, Gallo G, Albano L, Crisci D, Mazzaccara C, Strisciuglio P, Ruoppolo M, et al. Variants in GSTZ1 Gene Underlying Maleylacetoacetate Isomerase Deficiency: Characterization of Two New Individuals and Literature Review. Genes. 2025; 16(9):1009. https://doi.org/10.3390/genes16091009

Chicago/Turabian Style

Barretta, Ferdinando, Fabiana Uomo, Alessandra Verde, Mariagrazia Fisco, Giovanna Gallo, Lucia Albano, Daniela Crisci, Cristina Mazzaccara, Pietro Strisciuglio, Margherita Ruoppolo, and et al. 2025. "Variants in GSTZ1 Gene Underlying Maleylacetoacetate Isomerase Deficiency: Characterization of Two New Individuals and Literature Review" Genes 16, no. 9: 1009. https://doi.org/10.3390/genes16091009

APA Style

Barretta, F., Uomo, F., Verde, A., Fisco, M., Gallo, G., Albano, L., Crisci, D., Mazzaccara, C., Strisciuglio, P., Ruoppolo, M., Fecarotta, S., Parenti, G., Frisso, G., & Rossi, A. (2025). Variants in GSTZ1 Gene Underlying Maleylacetoacetate Isomerase Deficiency: Characterization of Two New Individuals and Literature Review. Genes, 16(9), 1009. https://doi.org/10.3390/genes16091009

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