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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2014

Open Access 01-12-2014 | Research

Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment

Authors: Catia Cavicchi, Maria Alice Donati, Rossella Parini, Miriam Rigoldi, Mauro Bernardi, Francesca Orfei, Nicolò Gentiloni Silveri, Aniello Colasante, Silvia Funghini, Serena Catarzi, Elisabetta Pasquini, Giancarlo la Marca, Sean David Mooney, Renzo Guerrini, Amelia Morrone

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

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Abstract

Background

X-linked Ornithine Transcarbamylase deficiency (OTCD) is often unrecognized in adults, as clinical manifestations are non-specific, often episodic and unmasked by precipitants, and laboratory findings can be normal outside the acute phase. It may thus be associated with significant mortality if not promptly recognized and treated. The aim of this study was to provide clues for recognition of OTCD in adults and analyze the environmental factors that, interacting with OTC gene mutations, might have triggered acute clinical manifestations.

Methods

We carried out a clinical, biochemical and molecular study on five unrelated adult patients (one female and four males) with late onset OTCD, who presented to the Emergency Department (ED) with initial fatal encephalopathy. The molecular study consisted of OTC gene sequencing in the probands and family members and in silico characterization of the newly detected mutations.

Results

We identified two new, c.119G>T (p.Arg40Leu) and c.314G>A (p.Gly105Glu), and three known OTC mutations. Both new mutations were predicted to cause a structural destabilization, correlating with late onset OTCD. We also identified, among the family members, 8 heterozygous females and 2 hemizygous asymptomatic males. Patients' histories revealed potential environmental triggering factors, including steroid treatment, chemotherapy, diet changes and hormone therapy for in vitro fertilization.

Conclusions

This report raises awareness of the ED medical staff in considering OTCD in the differential diagnosis of sudden neurological and behavioural disorders associated with hyperammonemia at any age and in both genders. It also widens the knowledge about combined effect of genetic and environmental factors in determining the phenotypic expression of OTCD.
Appendix
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Metadata
Title
Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment
Authors
Catia Cavicchi
Maria Alice Donati
Rossella Parini
Miriam Rigoldi
Mauro Bernardi
Francesca Orfei
Nicolò Gentiloni Silveri
Aniello Colasante
Silvia Funghini
Serena Catarzi
Elisabetta Pasquini
Giancarlo la Marca
Sean David Mooney
Renzo Guerrini
Amelia Morrone
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-014-0105-9

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