Atypical form of pediatric diabetes due to SLC29A3 mutation: Insights from two cases of H syndrome

The SLC29A3 mutation is known to cause a heterogeneous group of autoinflammatory syndromes, commonly referred to as H syndrome, with histiocytosis as the key pathology and diabetes as one of its features. We present two cases of H syndrome: one newly diagnosed at our institution and another previously diagnosed, presenting for follow-up. The first one is a 6-year-old girl who visited the endocrinology outpatient department. She had poorly controlled blood glucose levels, along with hyperpigmentation and hypertrichosis of the skin, predominantly over the lower limbs. Unlike typical type 1 diabetes mellitus, she required unusually high doses of insulin for glycemic control during hospitalization, making the case challenging to manage. Whole-exome sequencing revealed a mutation in the SLC29A3 gene at exon 6 on chromosome 10, which confirmed the diagnosis of H syndrome. The second case is a 21-year-old male with a genetically confirmed diagnosis of H syndrome, who presented to our center for blood glucose management. In contrast to the first patient, his characteristic skin changes appeared 4 years after the onset of diabetes. He had previously received multiple treatments, including methotrexate, hydroxychloroquine, and tofacitinib, with no significant impact on his clinical course. Just like the heterogeneity in the clinical manifestations, the severity of diabetes in H syndrome is highly variable, sometimes posing great difficulty in achieving optimal glycemic control. Although rare, with more cases being reported in the literature, it is crucial for endocrinologists to be aware of the condition.