c-peptide and Wolfram-Syndrome

Wolfram syndrome (WS), also known as a DIDMOAD (diabetes insipidus, early-onset diabetes mellitus, optic nerve atrophy and deafness) is a rare autosomal disorder caused by mutations in the Wolframin1 (

Topics: Animals; C-Peptide; Diabetes Mellitus, Experimental; Disease Models, Animal; Glucagon-Like Peptide-1 Receptor; Hearing Loss, Sensorineural; Liraglutide; Male; Nerve Degeneration; Optic Nerve; Phenotype; Rats; Visual Pathways; Wolfram Syndrome

The aim of the present paper is to describe a novel missense mutation (G107R) of WFS1 gene that was unexpectedly detected, in two siblings from Southern Italy, outside exon 8; a very unusual finding which has previously been reported only twice in Italian patients with Wolfram syndrome (WS). Although in Spanish pedigrees' WFS1 mutations are frequently located in exon 4, this finding is very infrequent in other pedigrees, particularly in Italian patients.. a) our report of two siblings with one novel WSF1 mutation (G107R) expands the molecular spectrum of WS; b) this is the 3rd report of Italian patients harbouring one mutation outside exon 8 and the 2nd with one mutation in exon 4; c) on the basis of the present observations, and literature data we can infer that mutation locations outside exon 8 do not seem to be clearly associated with peculiar phenotype expressions of WFS1 gene.

Topics: Base Sequence; C-Peptide; Child; Exons; Female; Genotype; Glycated Hemoglobin; Humans; Italy; Male; Membrane Proteins; Mutation; Phenotype; Siblings; White People; Wolfram Syndrome

Two girls with DIDMOAD syndrome are presented. One also had severe megaloblastic-sideroblastic anaemia and the other several neurological manifestations. Both were short with defective growth hormone secretion. Computed tomography revealed empty sella in both girls; one had widespread atrophic cortical and cerebellar changes. High doses of thiamine improved the anaemia in the first case, increased C peptide secretion in both, but had no effect on the neurological abnormalities.

Topics: Anemia, Sideroblastic; C-Peptide; Empty Sella Syndrome; Female; Growth Hormone; Humans; Infant; Nervous System Diseases; Thiamine; Tomography, X-Ray Computed; Wolfram Syndrome

We describe five patients with Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). Three of the patients appear to have had very gradual onset of diabetes mellitus at an early age yet all patients when tested for C-peptide response to glucagon were severely deficient. All patients are registered blind from primary optic atrophy, two have severe hearing difficulties and three high tone sensorineural hearing loss on audiometry. Four patients have cranial diabetes insipidus which in two cases is partial and of gradual onset and was attributed to poor control of the diabetes mellitus. In one case treatment of the insipidus relieved enuresis. All five patients have evidence of dilatation of the urinary tract and one patient is managed in the long-term by self-catheterisation which has resulted in one episode of bacteraemia. One patient has marked testicular atrophy and investigation reveals this to be due to primary hypogonadism and not to hypothalamic-pituitary dysfunction. One female patient had her menarche delayed until the age of 19 years but has subsequently had the only successful pregnancy in a patient with this syndrome of which we are aware.

Topics: Adolescent; Adult; Audiometry; Blindness; C-Peptide; Diabetes Insipidus; Female; Humans; Long-Term Care; Male; Menarche; Pregnancy; Puberty; Testicular Diseases; Urinary Catheterization; Urography; Wolfram Syndrome