若年発症型両側性感音難聴

Wolfram syndrome is a rare autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD). We present the case of a 19-year-old male with a history of juvenile-onset non-autoimmune diabetes mellitus who presented with fever, chills, seizures, altered sensorium, vomiting, and abdominal pain. The patient was treated for a hyperosmolar hyperglycemic state precipitated by gastrointestinal infection with intravenous fluids, antibiotics, and insulin therapy. Physical examination revealed short stature, delayed secondary sexual characteristics, neck rigidity, and bilateral upward plantar reflexes. Further neuroimaging revealed pontine atrophy, partial central diabetes insipidus, and bilateral optic atrophy. Fundoscopy confirmed optic disc pallor and generalized visual field loss. Pure tone audiometry indicated profound bilateral high-frequency sensorineural hearing loss, and magnetic resonance (MR) urography findings were consistent with a neurogenic bladder. His sensorium and neurological deficits improved within 3 days, and he was later discharged with close follow-up by a multidisciplinary team. This case highlights the classic presentation of Wolfram syndrome in a young male with diabetes and neurological complications, emphasizing the need for early recognition and multidisciplinary management. Wolfram syndrome poses significant diagnostic challenges due to its varied and progressive symptoms, and this report aims to contribute to the existing knowledge base and create awareness about the condition, its clinical presentation, and the need for a multidisciplinary management approach.

INTRODUCTION: Wolfram syndrome, a rare autosomal recessive disorder, is characterised by diabetes insipidus, juvenile diabetes mellitus, optic nerve atrophy and deafness (DIDMOAD). CASE REPORT: We present a case of a 21-year-old male diagnosed with Wolfram syndrome who underwent cochlear implantation due to progressive hearing loss. The patient first complained of bilateral hearing loss at the age of 8 years. As the hearing loss progressed hearing aids provided minimal benefit. A multidisciplinary team evaluated his extensive medical history, which included juvenile-onset diabetes mellitus, seizures, vision abnormalities and hypergonadotrophic hypogonadism. Pure tone audiometry was done which showed sloping bilateral severe to profound hearing loss, more at higher frequencies. Hrct and Mri temporal bone showed normal cochlear architecture and cochlear nerve. The patient received a Nucleus Profile™ CI 632 cochlear implant. Postoperative evaluation revealed significant improvement, with a speech discrimination score of 90% at the most comfortable level three months post-implantation. CONCLUSION: Wolfram syndrome is a rare genetic disorder with multisystem involvement and debilitating symptoms. High-frequency sensorineural hearing loss is a common association and hearing rehabilitation using hearing aids and cochlear implants must be considered to improve the quality of life.

INTRODUCTION: Wolfram Syndrome (WS) is a rare autosomal recessively inherited disorder characterized by juvenile-onset diabetes mellitus (DM), diabetes insipidus, optic atrophy (OA), hearing loss and neurodegeneration. This report describes three cases with WS. CASE REPORT: The first case was diagnosed with DM and OA at the age of 6 and 11 years, respectively. Second patient was the sibling of the first patient, also had DM and was investigated for WS after his brothers' diagnosis. The third patient was diagnosed with DM at the age of 5 years and developed bilateral sensorineural hearing loss and OA at the ages of 7 and 12 years, respectively. Preliminary diagnoses of all patients were confirmed by Sanger sequencing of the WFS1 gene. Two previously reported and a novel mutation were detected. While our first patient was diagnosed with attention deficit hyperactivity disorder previously described in WS patients, obsessive compulsive disorder observed in case 2, was not previously reported in WS to the best of our knowledge. Puberty delay was detected in our first patient and was diagnosed as constitutional delay of puberty and growth. CONCLUSION: Early diagnosis of WS can lead to early detection of associated pathologies and to decrease complications, morbidity and mortality.

PURPOSE: Wolfram syndrome is a rare genetic disorder characterized by juvenile onset of diabetes mellitus with bilateral optic atrophy. We report a case of adult onset Wolfram syndrome with diabetes mellitus at age 22 and optic atrophy after age 40. The WFS1 gene sequence was analyzed in the patient and her father. OBSERVATIONS: A 46-year-old woman presented with bilateral vision loss. She had developed diabetes mellitus at age 22 and underwent bilateral cataract surgery at age 37. Visual acuity was 20/50 in the right eye and 20/200 in the left eye. The pupillary light reflex was sluggish in both eyes. Fundus examination showed bilateral optic atrophy, but there was no diabetic retinopathy. Cecocentral scotoma of both eyes was observed in Goldmann perimetry. There were no intracranial lesions on magnetic resonance imaging. Audiometry demonstrated high-frequency sensorineural hearing loss. Sequence analysis of the WFS1 gene revealed compound heterozygous mutation: c.908T>C p.L303P and c.1232_1233del, p.S411Cfs*131 in the patient and heterozygous mutation c. 908 T>C, p. L303P in her father. CONCLUSIONS AND IMPORTANCE: The patient was diagnosed with adult-onset Wolfram syndrome with compound heterozygous mutations of the WFS1 alleles. Wolfram syndrome must be ruled out even in adult-onset diabetic patients with optic atrophy.

We describe a novel mitochondrial variant (m.5865 T > C) in a patient with decreased exercise endurance and juvenile onset slowly progressive bilateral ptosis without ophthamloparesis. The m.5865 T > C variant was seen in 82.9% of mtDNA molecules in skeletal muscle tissue and ~8% of mtDNA molecules in urine epithelium, but was not detected in blood leukocytes. The proband does not demonstrate any additional features often seen in individuals with a mitochondrial disorder (i.e., sensorineural hearing loss, type 2 diabetes, stroke-like episodes, muscle weakness, ophthalmoparesis, cardiomyopathy or cardiac arrhythmias). This case suggests that ptosis and exercise intolerance, without ophthalmoparesis, are the primary clinical features of the m.5865 T > C mtDNA variant.