LETTER TO THE EDITOR
Ornithine transcarbamylase (OTC) deficiency based
on a hemizygous p.R277W mutation causing life-threatening
hyperammonemic crisis during treatment
for Hodgkin’s lymphoma
Ellen Ritter
&
Ralf A. Husain
&
Katrin Hinderhofer
&
Tino Prell
&
Hans-Jörg Fricke
&
Sebastian Scholl
&
Andreas Hochhaus
&
Paul La Rosée
Received: 6 October 2010 / Accepted: 9 October 2010 / Published online: 9 November 2010
#
Springer-Verlag 2010
Dear Editor,
We report a rare case of ornithine transcarbamylase (OTC)
deficiency as origin for life-threatening hyperammonemia
in a young adult male patient with Hodgkin’s lymphoma.
Clinical case report
The reported patient was diagnosed with mediastinal
Hodgkin’s lymphoma (Ann Arbor stage IA) at the age of
23 years in November 2008. He underwent initial remission
induction with chemotherapy (doxorubicin, bleomycin,
vinblastine, dacarbazine) and involved field irradiation. In
April 2009, early relapse (stage IIA) caused upper airway
obstruction. Immediate treatment with intravenous predniso-
lone (continued with methylprednisolone p.o.) and irradiation
was initiated. Four weeks later, the patient presented with
reduced vigilance finally progressing to coma. Blood testing
revealed markedly elevated plasma ammonia levels
(>400 μmol/l, reference range [RR] 16–48 μmol/l; Fig. 1);
bilirubin and aminotransferases were marginally elevated.
Electroencephalography displayed a moderately severe
general alteration suggestive of metabolic encephalopathy.
Cranial magnetic resonance imaging (MRI) showed
slight cerebral edema and bilateral subcortical FLAIR
hyperintensities in the precentral region with patchy
distribution. Cerebrospinal fluid analysis, liver MRI and
histology, drug and medication screening as well as
microbiological investigations were negative. Corticosteroids
were discontinued, and the patient recovered completely
without extensive anti-hyperammonemic therapy. In June
2009, chemotherapeutic treatment of relapse was initiated
with dexamethasone, cytarabine, and cisplatin (DHAP) and
switched to the dexamethasone, carmustine, etoposide,
cytarabine, and melphalan (Dexa-BEAM) regimen due
to refractory disease. Twelve days after the onset of
Dexa-BEAM, the patient again presented with nausea,
vomiting, and progressive loss of vigilance. He was
transferred to the intensive care unit for transient
mechanic ventilation. Blood testing revealed severe
hyperammonemia (Fig. 1), reduced citrulline (13 μmol/l,
RR 19–55 μmol/l) and slightly elevated alanine levels
(622 μmol/l, RR 241–597 μmol/l) pointing to a possible
block of ureagenesis at the level of or proximal to OTC.
Other plasma amino acids (including arginine and
glutamine) and urinary orotic acid were in the reference
range. Blood glucose, lactate, carnitine, acylcarnitines,
and urinary organic acids were normal. Accordingly,
severe hepatic failure, organoacidurias, and disorders of
fatty acid oxidation appeared unlikely. Molecular analysis
E. Ritter
:
H.-J. Fricke
:
S. Scholl
:
A. Hochhaus
:
P. La Rosée (*)
Abteilung Hämatologie und Onkologie,
Klinik für Innere Medizin II, Universitätsklinikum Jena,
07747 Jena, Germany
e-mail: paul.larosee@med.uni-jena.de
R. A. Husain
Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Jena,
Jena, Germany
T. Prell
Hans-Berger-Klinik für Neurologie, Universitätsklinikum Jena,
Jena, Germany
K. Hinderhofer
Institut für Humangenetik, Universität Heidelberg,
Heidelberg, Germany
Ann Hematol (2011) 90:857–859
DOI 10.1007/s00277-010-1106-y