Volume 72, Issue 9, November 2025, 501534Author links open overlay panel, , , , , , , , , , , , Abstract

This is the case of a man with hepatorenal tyrosinemia type 1 (HT-1). Following the omission of his usual treatment with nitisinone and the withdrawal of dietary recommendations, the patient developed a severe neurological crisis requiring admission to the intensive care unit (ICU) due to profound diaphragmatic weakness. Despite the initial severity, appropriate management led to a favorable outcome and, eventually, weaning from mechanical ventilation. This case underscores the critical importance of a multidisciplinary approach in the management of inborn errors of metabolism, where nutritional therapy remains the cornerstone of treatment to prevent life-threatening complications.

Resumen

Se presenta el caso de un paciente adulto varón con tirosinemia hepatorrenal tipo 1 (TH-1). Tras la omisión de su tratamiento habitual con nitisinona y el abandono de las recomendaciones dietéticas, el paciente desarrolló una crisis neurológica grave que requirió ingreso en la Unidad de Cuidados Intensivos (UCI) debido a una debilidad diafragmática severa. A pesar de la gravedad inicial, el manejo adecuado permitió una evolución favorable, con la retirada progresiva de la ventilación mecánica. Este caso pone de manifiesto la importancia crítica de un abordaje multidisciplinar en el manejo de los errores innatos del metabolismo, donde la terapia nutricional continúa siendo una piedra angular del tratamiento para prevenir complicaciones potencialmente mortales.

Section snippetsCase presentation

This is the case of a 28-year-old man with a 2-year history of tyrosinemia type 1 (HT-1) after evidence of impaired liver function tests and proximal renal tubular dysfunction, with genetic analysis revealing the IVS8-1 (G>A) mutation. He was being followed by the pediatric metabolic disorders unit of our center until 2018, when he transitioned to the adult unit at the age of 18 years. However, years later he moved to a different region and stopped attending regular metabolic consultations

Management and evidenceHT-1 (OMIM #276700) is a rare inherited metabolic disorder characterized by a deficiency of fumarylacetoacetate hydrolase (FAH), which is essential in the tyrosine metabolic pathway. This deficiency leads to the accumulation of toxic metabolites, causing severe damage to diverse organs (Fig. 2). Before the introduction of specific pharmacological treatments, management was limited to a strict diet low in Tyr and Phe.

The real breakthrough in the treatment of HT-1 came with the introduction of

Areas of uncertainty

The mechanisms determining the severity and duration of neurological crises in HT-1 remain unclear. While some patients recover rapidly, others experience prolonged impairment despite early treatment. Further studies are needed to identify predictors of crisis duration and develop strategies for optimizing long-term neurological recovery.

Guidelines

This case report has been structured based on current evidence and expert recommendations for the management of HT-1. The Canadian consensus clinical practice guidelines provide the foundation for treatment, emphasizing NTBC therapy and dietary management as essential measures. Additionally, various studies on neurological crises and their progression were considered to assess treatment response.

Conclusions and recommendations

In patients with HT-1, discontinuation of standard treatment can lead to severe, potentially life-threatening neurological crises. Early reintroduction of NTBC and a specific diet, along with ventilatory support and rehabilitation, is essential for recovery, though improvement may be slow and hospital stays prolonged. Therefore, maintaining strict adherence to treatment and regular follow-up is strongly recommended to prevent such complications.

Authors’ contributions

All authors contributed to the drafting of the clinical case.

Informed consent statement

Explicit consent was obtained from the patient for the reporting of this case report, and this has been duly documented in the patient's electronic health record.

Ethics statement

Informed consent was obtained from the patient.

Funding

None declared.

Conflicts of interest

None declared.

Data availability statement

For further information regarding data related to the described case, the corresponding author can be contacted.

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© 2025 Published by Elsevier España, S.L.U. on behalf of SEEN and SED.