Unusual association of neurofibromatosis type I
and coeliac disease in a single patient
Federico Biagia
Jonia Campanellaa
Costanza Alvisib
Maurizio Versinoc
Gino Roberto Corazza a
a diarrhoea, steatorrhoea, and weight loss (7). It must,
Gastroenterology Unit, S. Matteo Hospital, University of
Pavia, Italy
b frank malabsorption.
Endoscopy Unit, S. Matteo Hospital, University of Pavia,
Italy
c patients affected by CD. Electrolyte and metabolic defi-
Department of Neurological Sciences, C. Mondino Insti-
tute of Neurology, University of Pavia, Italy
Reprint requests to: Dr Federico Biagi
Gastroenterology Unit
IRCCS Policlinico San Matteo
P.le Golgi, 19 - 27100 Pavia - Italy
E-mail: f.biagi@smatteo.pv.it
Accepted for publication: January 11, 2005
Summary
Twenty-five per cent of patients with neurofibromatosis
type 1 (NF1) have gastrointestinal involvement and mal-
absorption symptoms have been reported. We de-
scribe, for the first time, a patient with NF1, in whom
gastrointestinal symptoms were due to coeliac disease
(CD). Although this could be a coincidental association,
we suggest that CD should be taken into account in the
differential diagnosis of diarrhoea occurring in NF1 pa-
tients.
KEY WORDS: coeliac disease, malabsorption, neurofibromatosis
type 1.
Introduction
Von Recklinghausen’s neurofibromatosis or neurofibro-
matosis type 1 (NF1) is a relatively common autosomal
dominant disease (1/3000), characterized by multiple
neurofibromas arising in peripheral nerves at any site,
including the gastrointestinal tract (1). Submucosal neu-
rofibromas of the digestive tract were demonstrated in
25% of patients with NF1 (2). Although such an involve-
ment is usually asymptomatic (3), abdominal pain, dys-
pepsia, bleeding, or frank malabsorption symptoms (i.e.,
diarrhoea, steatorrhoea, and weight loss) can occur in
NF1 patients (4). These symptoms have several expla-
nations. Periampullary duodenal or pancreatic tumours
can obstruct pancreatic and/or biliary ducts (5); infiltrat-
ing mesenteric neurofibromas can cause lymphatic
Functional Neurology 2005; 20(1): 33-34
and/or vascular obstruction leading not only to a malab -
sorption syndrome but also to bowel ischaemia and/or
protein-losing enteropathy (6).
Coeliac disease (CD) is a chronic but reversible en-
teropathy due to gluten, the water-soluble fraction of
wheat flour proteins. In its major form, it can present with
therefore, be excluded in any patients suffering from
Several neurological disorders have been described in
ciencies may play a role in the development of neurolog-
ical deficits such as mixed peripheral neuropathy,
paraesthesiae, cerebellar ataxia, dementia, and mi-
graine (8,9). A close association between CD and neu-
rological diseases was demonstrated in epilepsy with
cerebral calcifications. CD was shown in 77.4% of pa-
tients affected by epilepsy with cerebral calcifications
(10). Finally, many case reports describe neurological
diseases occurring in CD patients. However, there is not
enough evidence to support the hypothesis that CD can
be associated with brain atrophy, multiple sclerosis, or
meningitis (8).
Although CD is a very common condition (11) and is as-
sociated with several neurological conditions (8-10,12),
it does not seem to have been described in NF1 patients
so far. We describe here a patient with NF1, in whom
gastrointestinal symptoms were due to CD.
Case report
In November 2001 a 39-year-old man with NF1 was ad-
mitted to our inpatient clinic because of diarrhoea, weight
loss, and distal muscle tetany. NF1 had been diagnosed
at the age of 28 years on the basis of multiple café-au-
lait spots (> 1.5 cm) and multiple subcutaneous neurofi-
bromas (1). NF1 genetic defects were not investigated.
Five years later he sustained a right above-the-knee am-
putation close to the hip because of a malignant periph-
eral nerve-sheath tumour of the calf. On admission,
physical examination revealed diffuse café-au-lait spots
and multiple subcutaneous lesions; malnutrition was ev-
ident (height 1.69 m; body weight 39 kg; body mass in-
dex 16.8 after correction for amputation). Hepatomegaly
was absent and there were no palpable masses in the
abdomen. However, a 4 cm nodule was present in the
right groin. Computed tomography and ultrasonography
showed that the groin nodule was likely due to schwan-
noma lymph node metastasis. On the other hand, neither
neurofibromas of the intestinal wall nor abdominal mass-
es were detected; liver, biliary tract and pancreas were
normal. Laboratory tests showed severe hypocalcaemia
(5.8 mg/dL) and hypomagnesaemia (1.2 mmol/L). Full
blood count, total serum proteins, albumin, liver function
33
F. Biagi et al.
tests and amylase were normal. Stool microscopy and
culture excluded intestinal infection. On the basis of mul-
tiple duodenal biopsies showing severe villous atrophy
and positive endomysial antibodies the patient was
found to be affected by CD (7). Furthermore, duodenal
biopsies excluded degenerative changes or fibrosis of
small arteries. Agluten-free diet was started. We saw the
patient again twelve months later. Diarrhoea and tetany
had stopped and the weight loss had been recovered.
Calcium and magnesium supplementation were no
longer necessary. The groin nodule had been surgically
removed and schwannoma was shown on histology. In
August 2002, he was started on chemotherapy because
of schwannoma pulmonary metastases found on a fol-
low-up chest X-ray. In September 2003, his body weight
was 55.0 kg (body mass index 23.6) and his gastroin-
testinal conditions were good.
Discussion
NF1 patients can frequently complain of gastrointestinal
symptoms, for which there can be varying explanations
(2,4-6). We have here described a patient whose gas-
trointestinal symptoms were due to CD. The diagnosis
was based on accepted histological and serological cri-
teria (7). Moreover, computed tomography, ultrasonog-
raphy and duodenal biopsy excluded other conditions as
responsible for these symptoms. Finally, the excellent
clinical response to a gluten-free diet further confirmed
that the patient was suffering from CD.
As far as we know, this is the first report of a patient af-
fected by both NF1 and CD. Since both NF1 and CD are
rather common conditions, we feel that that is probably
a coincidental association and that the two conditions
are not associated with each other. However, only a
serological search for coeliac antibodies in an adequate
number of NF1 patients would conclusively establish
whether the two conditions are associated. In our view,
this case indicates that the diagnosis of CD should al-
ways be taken into account in any NF1 patient suffering
from gastrointestinal symptoms.
34
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