Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency - a case report.

We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes.

Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion.

OBJECTIVE: Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide. RESEARCH DESIGN AND METHODS: To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5'-triphosphate inhibition were associated with the most severe neurologic symptoms. CONCLUSIONS: We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.