Wolfram (DIDMOAD) syndrome: a multidisciplinary clinical study in nine Turkish patients and review of the literature.
OBJECTIVE
To study Wolfram syndrome (WFS) with multidisciplinary consultations and compare the results with the literature.


METHODS
Nine patients fulfilled the ascertainment criteria of WFS (insulin-dependent diabetes mellitus and optic atrophy). All patients were evaluated by the departments of paediatrics, ophthalmology, audiology, urology and medical biology.


RESULTS
The earliest manifestation of WFS was insulin-dependent diabetes mellitus (at a median age of 6.9 y), followed by optic atrophy (8.9 y), diabetes insipidus (10.2 y) and deafness (10.5 y). Short stature was found in five cases, delayed puberty in two cases and hypergonadotropic hypogonadism in one case. Audiography disclosed hearing loss at high frequency in all patients (100%), but only five patients had clinical subjective hearing problems. Intravenous pyelography revealed hydroureteronephrosis in eight patients. Urodynamics revealed a normal bladder in only one patient. Three patients had a low-capacity, low-compliance bladder, detrusor external sphincteric dyssynergia and emptying problem, while five had an atonic bladder. Ocular findings were optic atrophy, low visual acuity and colour vision defects. Visual field tests revealed concentric and/or peripheral diminution in five patients. Visual evoked potentials were abnormal (reduced amplitude to both flash and pattern stimulation) in seven patients. Cranial magnetic resonance imaging showed mild or moderate atrophy of the optic nerves, chiasm, cerebellum, basal ganglia and brainstem in six patients; there was a partially empty sella in one case. There was no evidence of mitochondrial tRNA(Leu) (UUR) A to G (nucleotide 3243) mutation.


CONCLUSIONS
Wolfram syndrome should be evaluated in a multidisciplinary manner. Some specific and dynamic tests are necessary to make a more precise estimate of the prevalence and median age of the components of WFS. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotropic. Bladder dysfunction does not always present as a large atonic bladder in WFS. A low-capacity, high-pressure bladder with sphincteric dyssynergia is also common.
Simsek
E
E
Department of Paediatric Endocrinology, Abant Izzet Baysal University School of Medicine, Duzce, Turkey. esimsek@ibuduzce-tip.edu.tr
Simsek
T
T
Tekgül
S
S
Hosal
S
S
Seyrantepe
V
V
Aktan
G
G
D000293:Adolescent; D002648:Child; D003638:Deafness / Q000150:complications; D003919:Diabetes Insipidus / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009896:Optic Atrophy / Q000150:complications; D010348:Patient Care Team; D015995:Prevalence; D014421:Turkey / Q000453:epidemiology; D014792:Visual Acuity / Q000502:physiology; D014929:Wolfram Syndrome / Q000453:epidemiology / Q000235:genetics*
D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone