Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. The clinical presentation in female manifesting carriers varies both in onset and severity. We report on a female with insulin dependent diabetes mellitus and recurrent episodes of hyperammonemia. Since OTC activity me...

Descripción completa

Detalles Bibliográficos
Autores principales: Grünert, Sarah C, Villavicencio-Lorini, Pablo, Wermuth, Bendicht, Lehnert, Willy, Sass, Jörn Oliver, Schwab, K Otfried
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706312/
https://www.ncbi.nlm.nih.gov/pubmed/23829977
http://dx.doi.org/10.1186/2251-6581-12-37
_version_ 1782476534619045888
author Grünert, Sarah C
Villavicencio-Lorini, Pablo
Wermuth, Bendicht
Lehnert, Willy
Sass, Jörn Oliver
Schwab, K Otfried
author_facet Grünert, Sarah C
Villavicencio-Lorini, Pablo
Wermuth, Bendicht
Lehnert, Willy
Sass, Jörn Oliver
Schwab, K Otfried
author_sort Grünert, Sarah C
collection PubMed
description Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. The clinical presentation in female manifesting carriers varies both in onset and severity. We report on a female with insulin dependent diabetes mellitus and recurrent episodes of hyperammonemia. Since OTC activity measured in a liver biopsy sample was within normal limits, OTC deficiency was initially excluded from the differential diagnoses of hyperammonemia. Due to moderately elevated homocitrulline excretion, hyperornithinemia-hyperammonemia-homocitrullinuria-syndrome was suggested, but further assays in fibroblasts showed normal ornithine utilization. Later, when mutation analysis of the OTC gene became available, a known pathogenic missense mutation (c.533C>T) in exon 5 leading to an exchange of threonine-178 by methionine (p.Thr178Met) was detected. Skewed X-inactivation was demonstrated in leukocyte DNA. In the further clinical course the girl developed marked obesity. By initiating physical activities twice a week, therapeutic control of both diabetes and OTC deficiency improved, but obesity persisted. In conclusion, our case confirms that normal hepatic OTC enzyme activity measured in a single liver biopsy sample does not exclude a clinical relevant mosaic of OTC deficiency because of skewed X-inactivation. Mutation analysis of the OTC gene in whole blood may be a simple way to establish the diagnosis of OTC deficiency. The joint occurrence of OTC deficiency and diabetes in a patient has not been reported before.
format Online
Article
Text
id pubmed-3706312
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-37063122013-07-15 Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management Grünert, Sarah C Villavicencio-Lorini, Pablo Wermuth, Bendicht Lehnert, Willy Sass, Jörn Oliver Schwab, K Otfried J Diabetes Metab Disord Case Report Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. The clinical presentation in female manifesting carriers varies both in onset and severity. We report on a female with insulin dependent diabetes mellitus and recurrent episodes of hyperammonemia. Since OTC activity measured in a liver biopsy sample was within normal limits, OTC deficiency was initially excluded from the differential diagnoses of hyperammonemia. Due to moderately elevated homocitrulline excretion, hyperornithinemia-hyperammonemia-homocitrullinuria-syndrome was suggested, but further assays in fibroblasts showed normal ornithine utilization. Later, when mutation analysis of the OTC gene became available, a known pathogenic missense mutation (c.533C>T) in exon 5 leading to an exchange of threonine-178 by methionine (p.Thr178Met) was detected. Skewed X-inactivation was demonstrated in leukocyte DNA. In the further clinical course the girl developed marked obesity. By initiating physical activities twice a week, therapeutic control of both diabetes and OTC deficiency improved, but obesity persisted. In conclusion, our case confirms that normal hepatic OTC enzyme activity measured in a single liver biopsy sample does not exclude a clinical relevant mosaic of OTC deficiency because of skewed X-inactivation. Mutation analysis of the OTC gene in whole blood may be a simple way to establish the diagnosis of OTC deficiency. The joint occurrence of OTC deficiency and diabetes in a patient has not been reported before. BioMed Central 2013-07-05 /pmc/articles/PMC3706312/ /pubmed/23829977 http://dx.doi.org/10.1186/2251-6581-12-37 Text en Copyright © 2013 Grünert et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Report
Grünert, Sarah C
Villavicencio-Lorini, Pablo
Wermuth, Bendicht
Lehnert, Willy
Sass, Jörn Oliver
Schwab, K Otfried
Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management
title Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management
title_full Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management
title_fullStr Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management
title_full_unstemmed Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management
title_short Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management
title_sort ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706312/
https://www.ncbi.nlm.nih.gov/pubmed/23829977
http://dx.doi.org/10.1186/2251-6581-12-37
work_keys_str_mv AT grunertsarahc ornithinetranscarbamylasedeficiencycombinedwithtype1diabetesmellitusachallengeinclinicalanddietarymanagement
AT villavicenciolorinipablo ornithinetranscarbamylasedeficiencycombinedwithtype1diabetesmellitusachallengeinclinicalanddietarymanagement
AT wermuthbendicht ornithinetranscarbamylasedeficiencycombinedwithtype1diabetesmellitusachallengeinclinicalanddietarymanagement
AT lehnertwilly ornithinetranscarbamylasedeficiencycombinedwithtype1diabetesmellitusachallengeinclinicalanddietarymanagement
AT sassjornoliver ornithinetranscarbamylasedeficiencycombinedwithtype1diabetesmellitusachallengeinclinicalanddietarymanagement
AT schwabkotfried ornithinetranscarbamylasedeficiencycombinedwithtype1diabetesmellitusachallengeinclinicalanddietarymanagement