CASE REPORT

Acute supporative osteomyelitis of the lower

jaw in Wolfram syndrome: Report of case
and review of literature
Hossein Mortazavi
a
, Hossein Shahoon
b
, Arash Khojasteh
a,
*
a
Department of Oral and Maxillofacial Surgery, Taleghani hospital, Beheshti University of
Medical Science, Tabnak Ave, Velengak, Tehran, Iran
b
Department of Oral and Maxillofacial Surgery, Shahed University of Medical Science, Iran
Received 14 May 2005; accepted 16 May 2005
Summary Wolfram syndrome is a rare, congenital, multisystem disorder believed
to be caused by both mitochondrial and nuclear gene dysfunction. Diabetes insipi-
dus, diabetes mellitus, and vision and hearing defects are the main symptoms asso-
ciated with this syndrome. Disorders of the urinary tract are also often present.
Wolfram syndrome affects males and females equally and may be inherited as an
autosomal recessive trait. Here in we report a patient with acute supporative oste-
omyelitis who suffered from wolfram syndrome. Correction of the baseline ketoac-
idotic situation and aggressive antiobiotic therapy lead to complete healing of the
lesion.

c
2005 Elsevier Ltd. All rights reserved.
KEYWORDS
Wolfram;
Diabete;
Osteomyelytis;
Syndrome
Introduction
Wolfram syndrome is an autosomal recessive neu-
rodegenerative disorder associated with juvenile
onset non-autoimmune diabetes and progressive
bilateral optic atrophy.
1,2
The WFS1 genes respon-
sible for Wolfram syndrome was discovered by a
positional cloning strategy.
7
Wolfram syndrome, or diabetes insipidus, diabe-
tes mellitus, optic atrophy disorder (DIDMOAD).
1
Wolfram patients demonstrate non-inammatory
atrophic changes in the brain
3
and in pancreatic is-
lets, resulting in progressive diabetes, blindness,
deafness, and other severe neurological defects.
4
Genetic analysis has demonstrated that mutations
in the WFS1 gene are clearly associated with the
DIDMOAD syndrome.
2,5
The Wolfram gene encodes
a 100-kDa tetrameric protein (wolframin) possess-
ing 910 predicted transmembrane segments.
6
However, no clear sequence similarities have been
identied that might shed light on the function of
1741-9409/$ - see front matter

c
2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ooe.2005.05.005
*
Corresponding author. Tel.: +98 912 1060032.
E-mail address: Arashkhojasteh@yahoo.com (A. Khojasteh).
Oral Oncology EXTRA (2005) 41, 191194
http://intl.elsevierhealth.com/journal/ooex
the protein.
7
Northern blot analysis has revealed
prominent expression of wolframin mRNA in af-
fected tissues, including the brain and pancreas.
3,7
These expression sites correlate well with the
atrophic changes associated with the syndrome.
It was suggested that wolframin may be a mito-
chondrial protein,
8
because many of the clinical
features characteristic of this syndrome are similar
to defects in oxidative phosphorylation that are
seen in mitochondrial diseases, such as mitochon-
drial encephalomyopathy, lactic acidosis, and
strokelike symptoms (MELAS), Lebers hereditary
optic neuropathy, and maternally inherited diabe-
tes and deafness (mitochondrial diabetes). Support-
ing this hypothesis, deletions of mitochondrial DNA
have been reported in some Wolfram patients.
9
Op-
tic neuropathy, diabetes insipidius accompany the
patient with Wolfram syndrome patients in almost
all of the cases.
4
Urinary tract complication, incon-
tinence and bed wetting also reported in some
cases.
10
neurologic complications such as severe
depression psycosis, or organic brain syndrome,
may be severe enough to require hospitalization.
Here in we report a case with wolfram syndrome
that acute supporative ostomyelitis was one of his
peculiar nding. The aim of the present report is
to alert physicians about the association between
the diabetes mellitus and supporative osteomyelitis
with the monogenic syndromes such as wolfram
syndrome, and to address the necessity of multi-
facet evaluation of patients.
Report of a case
A 20 year old man was referred to, Department of
Oral and Maxillofacial Surgery, Taleghani hospital,
Tehran, Iran on September 16, 2000. The patient
suffered from pain, slight swelling and white crea-
my discharge in the right buccal vestibular area.
Mild facial asymmetry was also noted (Fig. 1). He
had pain, tenderness and history of Root canal
therapy 45 days before the swelling initiated on
tooth number 30.
The patient had congenital nystagmus and his vi-
sual aquity decrease when he grew up. Since 2 years
ago the patient had no light perception. The medi-
cal history and consultation with endocrinologist
revealed that patient suffering from immature pup-
erty, polyphagia, polydypsia, polyurea, sensory
hearing loss, and dysuria. Initial clinical examina-
tion showed moderate weight loss (52 kg) and
recurrent fever during 2 weeks ago. Right mandibu-
lar hyposthesia was also noted by the patient. Sex
organ were undeveloped (Phallus was 4 cm at full
and testis size was about 1 2 1.5 cm). His
familial history revealed that the patient grand-
father died because of nephropathy associated
with diabetes mellitus at the age of 68.
There was tenderness in the right buccal mandib-
ular mucosa and active discharge of pus was pres-
ent. Radiographic evaluation showed ill dened
radiolucent lesion which reached to the inferior cor-
tical border of the right mandible (Fig. 2). There was
no opacication or lobulation in the lesion. An
appropriate endodontic treatment was seen in the
condemned tooth (Fig. 3). Routine laboratory inves-
tigation showed moderate leukocytosis, and in-
crease in sedimentation rate (ESR). Signicant
increasing in blood sugar accompanied with ketonu-
ria and the other sign and symptom of the patient,
conrmed the diagnosis of the acute supporative
osteomyelitis in the suggested wolfram syndrome
patient. Whole body bone scan with T
c
99 m re-
vealed increasing activity in the right mandibular
body region (Fig. 4). In conjunction with the depart-
ment of endocrinology the ketoacidotic condition of
the patient was corrected. Base on the antibiogram
culture and sensivity test pencillin G, 18 million/IU/
per day and cloxacillin, 2 g/per day was adminis-
tered for him. The acute supporative inammatory
condition of the bone healed after 4 weeks. The pa-
tient gave oral antibiotic regimen for 6 month after
Figure 1 Mild facial asymmetry in the right mandibular
body.
192 H. Mortazavi et al.
discharge. Two years follow up showed complete
healing of the left mandibular bone.
Discussion
Wolfram syndrome is a autosomal recessive
disorder dened by juvenile, insulin-dependent
diabetes mellitus and progressive optic atrophy,
with variable manifestations including deafness,
diabetes insipidus, cataracts, and neurologic
symptoms.
1,7
The gene responsible for Wolfram
syndrome is, WFS1, a member of a novel gene
family encoding an 890 amino acid glycopro-
tein with 910 predicted transmembrane
domains.
6,12,14
WS has been attributed to mutations in the WFS1
gene, which codes for a protein predicted to pos-
sess 910 transmembrane segments.
6,12
Little is
known concerning the function of the WFS1 protein
(wolframin). Wolframin thus appears to be impor-
tant in the regulation of intracellular Ca
2+
homeo-
stasis. Disruption of this function may place cells
at risk of inappropriate death decisions, thus
accounting for the progressive beta cell loss and
neuronal degeneration associated with the
disease.
11
Diabetes mellitus is usually the rst symptom to
present at a median age of 6 years, followed by
onset of optic atrophy at a median age of 11
years.
11,2
Optic atrophy was often detected at the same
time as diabetes or was symptomatic before the
onset of diabetes. Although visual acuity deterio-
rates mainly on the basis of optic atrophy, some
children may have an element of myopia, which
is correctable with eyeglasses. Deafness due to
high-tone hearing loss was reported in patients
with wolfram syndrome, and it can be a major clin-
ical problem.
8,10,12
Treatment of Wolfram syndrome is symptomatic
and supportive. Diabetes mellitus may be
controlled with a daily routine of insulin injections,
controlled diet, exercise to burn off glucose, and
frequent testing for blood sugar levels.
8,10,2
Otherwise, effective control of diabetes insipidus
may be obtained with several prescription
medications of the vasopressin hormone (ADH)
which are commercially available. These include
Lypressin (a synthetic vasopressin as a nasal spray)
and desmopressin acetate (a longer acting
synthetic ADH substitute
13
). Two types of drugs
have been found useful in reducing excessive
urination due to Diabetes Insipidus. These drugs
may reduce or eliminate the need for vasopressin
in some patients. For patients with diabetic reti-
nopathy, normalization of glucose levels in diabetic
patients can help reverse changes in the small
blood vessels of the eye. If normal glucose levels
can be maintained, this complication of diabetes
can be avoided. Normalization of glucose level in
our case and aggressive antibiotic therapy without
surgical intervention lead to complete healing of
lesion.
Figure 3 Periapical view of the teeth.
Figure 2 Ill dened radiolucent lesion was seen in the
posterior mandibular body area.
Figure 4 Greater absorbtion of T
c
99 m in the right
mandibular body.
Acute supporative osteomyelitis of the lower jaw in Wolfram syndrome 193
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