Background: Wolfram syndrome (WS) is a monogenic disorder associated with diabetes mellitus (DM), optic atrophy, diabetes insipidus (DI), neurological deterioration and deafness. Growth has been poorly characterised in case series.
Objective and hypotheses: To determine growth and prevalence of endocrine disorders, qualify therapies and metabolic outcome for DM, and relationship of cranial MRI findings to clinical findings in children and young people (CYP) with WS.
Method: Examination of records of CYP attending a nationally commissioned specialist clinic for WS from 20122015, to determine height, weight, BMI, history, DM therapy, DI, thyroid and pubertal disorders. Results of gonadotrophin, sex steroid levels, TFTs, HbA1c, blood glucose, paired early morning plasma and urine osmolality. Height, weight and BMI were converted to standard deviation scores using UK 1990 growth data. Cranial MRI reports were examined for pituitary abnormalities (PA).
Results: Mean height, weight and BMI SDS (SD) were −0.226 (0.98), 0.195 (0.74) and 0.427(0.88) respectively. No significant sex differences were present. DM was present in 89%. Median HbA1c was 8.0%, with 35.6% achieving target HbA1c <7.5% and 44% managed on intensive insulin therapy. Cranial MRI was successful in 68% of the cohort. DI was present in 39%. In patients with successful imaging posterior PA was present in 100% with DI, and 64% without DI. Two patients also had anterior PA without clinical evidence of anterior or posterior pituitary failure. Two CYP had hypergonadotrophic hypogonadism, requiring sex steroid replacement therapy.
Conclusion: This data implies CYP with WS demonstrate normal growth. It is concerning to see that although outcomes are better than average for all forms of DM, the majority of CYP are treated more frequently with non-intensive insulin regimes, and have suboptimal diabetes control. This should be a focus for improving future outcomes. Further studies are required to study evolution of PA in WS.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology