Endocrine Abstracts

Background: Wolfram Syndrome (WFS) is a rare genetic progressive neurodegenerative disorder caused by mutation in the gene encoding Wolframin, a protein located in the endoplasmic reticulum. WFS has an estimated prevalence of 1 in 770 000.The hallmark features are Diabetes Mellitus, Diabetes Insipidus, Optic Atrophy, Deafness(DIDMOAD) and neurodegeneration. Classic WFS1 is inherited in an Autosomal Recessive manner whereas the Non-classic form is Autosomal Dominant either from an affected parent or as a de novo mutation.

Case: We present a term female infant with normal antenatal history. She was confirmed to have Bilateral Sensorineural hearing loss soon after birth. Subsequent genetic testing for congenital deafness identified the infant to be heterozygous for the WFS1(c2425G>Ap.Glu809Lys) pathogenic variant indicating Wolfram like spectrum disorder(the rare non-classic form of WFS).The family were counselled that the development of any osmotic symptoms should prompt a clinical review. Now 18 months old, this Caucasian girl presented with osmotic symptoms of polyuria, polydipsia and weight loss. She was diagnosed with Diabetes Mellitus(blood glucose of 25 mmol/L).She was not in DKA (with a pH of 7.43).Investigations from a diabetes perspective demonstrated negative autoantibodies for GAD, IA2 and Zinc Transporter confirming she had an Insulin dependent non autoimmune diabetes, characteristic of WFS. There was no pathogenic variant detected in either of the parents which points towards a de-novo heterozygosity. She was initially managed with a combination of rapid (Aspart) and long acting(Degludec) insulin. Due to persistent episodes of hypoglycaemia, she was switched to ultra-rapid Aspart insulin analog, adjusted to the carbohydrate content, with a very good response. Transition to Insulin pump therapy and a hybrid closed loop system is being considered as an option for optimising diabetes care.

Conclusion: There is no cure for this condition. Supportive care is provided by MDT and regular surveillance is recommended for monitoring existing and emerging manifestation along with genetic counselling for future pregnancies. The WFS clinic for the whole of UK lies in two centres in Birmingham: Children’s hospital and Queen’s Elizabeth Hospital for paediatric and adult patients respectively.