An Asian Indian Woman with Wolfram Syndrome on Insulin Pump: Successful Pregnancy and Beyond

Abstract

Wolfram syndrome (WS), or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal recessive neurodegenerative disorder with a median life expectancy of 30 years and occurs in one in 770,000 live births. To date only five successful pregnancies have been reported among WS subjects worldwide. Here we describe the sixth report of successful pregnancy in a WS patient and the first from India. The subject is still on an insulin pump, now 31 years old and doing well. She developed diabetes at 5 years of age, optic atrophy at 14 years, and diabetes insipidus at 25 years and had a successful delivery in 2007 while on an insulin pump. Sequencing of exonic regions of the WFS1 gene showed five changes, two of which were pathogenic (exon 8). Magnetic resonance imaging of brain showed generalized neurodegenerative changes. The benefits of continuous subcutaneous insulin infusion and that of tight metabolic control in prevention of abortions and fetal malformations in diabetes associated with pregnancy are well documented. The impression of probable pleiotropic action of insulin pumps over and above that of glycemic reduction is gaining momentum. Recent evidence supports use of insulin pumps in alleviating neuropathic pain in diabetes, probably by virtue of its action in minimizing mean amplitude of glycemic excursions not possible with conventional insulin shots. WS is a progressive neurodegenerative disorder, which will probably help us in understanding the positive impact of continuous subcutaneous insulin infusion in prolonging the life span and retarding neuronal damage in WS.

Wolfram Syndrome 1 in Two Brothers Treated with Insulin Pump

“…There is only 1 previous case report of WS and insulin pump in 2011 that described the first case in India of a successful pregnancy in a WS patient; the authors described the benefits of continuous subcutaneous insulin infusion and tight metabolic control in the prevention of abortions and fetal malformations in DM associated with pregnancy and WS. 13 In our patients, despite having the same genetic variant, due to individual characteristics, the first patient was treated with SIIS, and the second with an insulin pump only. It is important to consider that treatment with an insulin pump has some benefits related to the patient’s adherence; however, individuals with neurodegeneration can report some difficulties, like in our WS patients who have had poor adherence to treatment, specifically in the daily use and care of the device.…”

Paediatric Wolfram syndrome Type 1: should gonadal dysfunction be part of the diagnostic criteria?

“…Moreover, pubertal delay is often observed in WFS1-SD adolescents alongside with growth delay due to concomitant hypopituitarism ( 15 , 23 ). Nevertheless examples of successful pregnancy and delivery have been described and first reports of male fertility date back to 2013 ( 15 , 24 , 25 ).…”

“…Nevertheless, cases of successful pregnancy and delivery exist and first reports of male fertility date back to a decade ago (15,24,25).…”