Mitochondrial neurogastrointestinal encephalomyopathy mimicking anorexia nervosa.
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ABSTRACT: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase and is characterized by external ophthalmoparesis, gastrointestinal dysmotility, leukoencephalopathy, and neuropathy. The availability of new therapeutic options (peritoneal dialysis, allogeneic stem cell transplantation, enzyme replacement) makes it necessary to diagnose the disease early, which is not always achieved due to the difficulty in recognizing this disorder, especially in case of atypical presentation. We describe three MNGIE patients with atypical onset of the disease. In the first patient the main symptoms were long-standing chronic fever, recurrent acute migrant arthritis, and gastrointestinal disorders mimicking autoimmune or inflammatory intestinal diseases; the second patient complained only of exercise intolerance and muscle cramps, and the third patient had a CIDP-like polyneuropathy. This study stresses the insidious heterogeneous clinical onset of some cases of MNGIE, expands the spectrum of the phenotype, and suggests considering MNGIE in the differential diagnosis of enteropathic arthritis, isolated exercise intolerance, and inflammatory polyneuropathies not responsive to the usual treatment. A better understanding of the clinical heterogeneity of MNGIE is necessary in order to diagnose atypical cases and promote early diagnosis, which is now absolutely necessary in view of the new available therapies.Journal of Inherited Metabolic Disease 04/2011; 34(6):1199-203. · 4.14 Impact Factor
Am J Psychiatry 166:4, April 2009
LETTERS TO THE EDITOR
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NORA PERRONE-BIZZOZERO, PH.D.
W. MICHAEL BULLOCK
The authors’ disclosures accompany the original article.
This letter (doi: 10.1176/appi.ajp.2009.09010011r) was ac-
cepted for publication in February 2009.
Encephalomyopathy Mimicking Anorexia
TO THE EDITOR: Mitochondrial neurogastrointestinal en-
cephalomyopathy is a rare autosomal recessive mitochon-
drial disorder caused by mutations in the thymidine phos-
phorylase gene (1). It is characterized by severe cachexia,
gastrointestinal dysmotility, progressive external ophthal-
moplegia, peripheral neuropathy, and diffuse leukoencepha-
lopathy on magnetic resonance imaging (MRI). The accumu-
lation of thymidine and deoxyuridines causes imbalances of
mitochondrial nucleotide pools that may lead to depletions
of mitochondrial DNA and multiple deletions (2). We present
the case of a patient with prominent cachexia in mitochon-
drial neurogastrointestinal encephalomyopathy mimicking
“Miss A” was a 21-year-old Indian woman diagnosed as
having treatment-resistant anorexia nervosa. She was re-
ferred to our department of psychiatry after her weight
decreased by 25 kg (body mass index: 11.6), despite re-
ceiving specific treatment in a psychosomatic hospital.
Miss A was thin and appeared to be growth-retarded.
She had a flat mood and showed infantile behavior. In ad-
dition to diffuse abdominal complaints, she had demon-
strated anorectic symptoms since puberty and had pecu-
liar, restrictive eating habits. Since a distorted body image
could not be clearly elicited, our working hypothesis re-
garding a diagnosis was atypical anorexia nervosa (ICD-10:
F50.1; DSM IV: 307.1).
The patient was unable to gain weight, despite her ef-
fort, solely by normal clinical support, such as structured
meals, psychotherapy, and additional medical treatment.
After placement of a gastric tube to provide high-caloric
nutrition, her clinical state rapidly worsened. She began
to vomit and experienced loud borborygmi, abdominal
pain, fever, and physical exhaustion.
A neurological examination revealed that the patient
had bilateral ptosis, infranuclear ophthalmoparesis, and
generalized areflexia. Her diagnostic work-up indicated
that lactate was increased two-fold above the upper limit
of normal in the serum and CSF. Her urine analysis for pu-
rines and pyrimidines yielded increased concentrations of
thymidine and deoxyuridine. Electromyography showed
marked demyelinating sensorimotor polyneuropathy, and
diffuse leukoencephalopathy was found by MRI (Figure 1).
A genetic analysis revealed a hitherto nondescribed ho-
mozygous mutation (c.605G>A,p.Arg202Lys) in the ECGF1
gene, which encodes for thymidine phosphorylase. This
mutation could not be detected in 68 healthy, ethnically
matched comparison subjects from India. Miss A was then
diagnosed as having mitochondrial neurogastrointestinal
With regard to the present case of prominent cachexia in
mitochondrial neurogastrointestinal encephalomyopathy
mimicking anorexia nervosa, we would like to emphasize that
syndromes of eating disturbances and cachexia could be the
most prominent features of a number of somatic and psychi-
atric disorders. In addition to prominent eating disturbance
in common psychiatric diseases such as anorexia nervosa,
depression, and schizophrenia, such behavior and symptoms
can also be prominent in mainly somatic disorders such as ju-
FIGURE 1. Diffuse Leukoencephalopathy in Patient Mim-
icking Anorexia Nervosaa
aThe magnetic resonance images illustrate increased signal intensity
(arrowheads). The images demonstrate diffuse leukoencephalopa-
thy with involvement of the A) centrum semiovale (axial T2-
weighted images), B) parts of the thalamus (axial T2-weighted im-
ages), C) internal capsule (coronal fluid-attenuated inversion recov-
ery images), and D) pons (sagittal T2-weighted images).
Am J Psychiatry 166:4, April 2009
LETTERS TO THE EDITOR
venile Alexander disease, Klinefelter’s syndrome, hypotha-
lamic brain tumors, Lyme disease, Crohn’s disease, celiac dis-
ease, achalasia, and Luft’s disease.
Thus, thorough clinical (particularly neurological) and bio-
chemical examinations (including CSF and urine analysis) to-
gether with MRI are essential to clearly differentiate between
psychiatric and somatic origins within the spectrum of
cachexia inducing disorders, especially in cases of atypical
anorexia nervosa, which lack cardinal symptoms (distorted
body image, intentional weight loss), and in cases in which
abdominal complaints may be prominent.
Our patient eventually received better absorbable high-ca-
loric nutrition via a gastric tube in addition to intravenous
feeding. These measures resulted in a weight gain to 28.6 kg
(body mass index: 12.7) and improvement of her physical
state, which remained stable 6 months following her dis-
charge from the hospital.
1. Lara MC, Valentino ML, Torres-Torronteras J, Hirano M, Martí R:
Mitochondrial neurogastrointestinal encephalomyopathy
(MNGIE): biochemical features and therapeutic approaches.
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2. Hirano M, Lagier-Tourenne C, Valentino ML, Marti R, Nishigaki
Y: Thymidine phosphorylase mutations cause instability of mi-
tochondrial DNA. Gene 2005; 354:152–156
BEREND FEDDERSEN, M.D.
LARISSA DE LA FONTAINE, M.D.
JÖRN OLIVER SASS, Dr. rer.nat.
JURGEN LUTZ, M.D.
ANGELA ABICHT, M.D.
THOMAS KLOPSTOCK, M.D.
ISHWAR CHANDER VERMA, M.D.
New Delhi, India
EVA MEISENZAHL, M.D.
OLIVER POGARELL, M.D.
Drs. Feddersen and de la Fontaine contributed equally to this
The authors report no competing interests.
This letter (doi: 10.1176/appi.ajp.2008.08101525) was accepted
for publication in November 2008.
Reprints are not available; however, Letters to the Editor can be downloaded at http://ajp.psychiatryonline.org.
In the article “Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disor-
der and Prediction of Treatment Response” by Jack B. Nitschke, Ph.D., et al. (published online January 2, 2009),
an error in the Journal’s editorial office resulted in the y coordinates of the right and left dorsal amygdala un-
der “ANOVA valence main effect” running without the negative signs in Table 2. The appropriate Talairach co-
ordinates are as follows:
ANOVA valence main effect
Right dorsal amygdala: 14, –6, –10
Left dorsal amygdala: –14, –2, –14
Left dorsal amygdala: –22, –9, –14
This change was made for the article’s appearance in the March 2009 print issue and the online posting as part
of the March issue, replacing the article posted January 2, 2009.
In the article “Competition and the Mental Health System” by Alison Evans Cuellar, Ph.D. and Deborah
Haas-Wilson, Ph.D. (Am J Psychiatry 2009 166: 278–283) the DOI is incorrect in the print edition. The full text
HTML and online PDF have been changed to reflect the correct DOI (doi: 10.1176/appi.ajp.2008.08091383).