An Unusual Syndromic Presentation in Diabetes: Histiocytosis-Lymphadenopathy Plus Syndrome

Histiocytosis-lymphadenopathy plus syndrome is a rare autosomal recessive multisystemic disorder caused by mutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3. This mutation has been linked to a group of syndromic histiocytoses including H-syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and familial Rosai-Dorfman disease.

We report the case of an 18-year-old woman from an Arab country with no parental consanguinity who presented to our department with uncontrolled diabetes, repeated severe hypoglycaemic episodes, short stature and delayed puberty. Her history included exocrine pancreatic insufficiency, marked skin hyperpigmentation with thickening of the lower limbs, skeletal deformities, chronic anaemia, impacted teeth and a constellation of findings strongly evocative of H-syndrome. In addition, she presented with multiple deep lymphadenopathies.

This case reflects the variable expression of H-syndrome. We report, for the first time, dental inclusion as a possible additional feature of this syndrome. The patient presented with a severe systemic form involving multiple organs, including pancreatic insufficiency, diabetes with persistent glycaemic instability despite multiple daily insulin injections and close monitoring, delayed puberty requiring initiation of transdermal oestradiol therapy, and dermatological manifestations poorly responsive to topical treatments. These findings underscore both the heterogeneity of clinical presentation and the challenges in managing H-syndrome.

With fewer than 100 cases described worldwide, histiocytosis-lymphadenopathy plus syndrome remains vastly underdiagnosed. This case highlights the importance of recognising its characteristic clinical features and aims to raise awareness among clinicians, encouraging them to consider uncommon diagnoses when faced with unusual combinations of dermatological, endocrine and skeletal signs.

Histiocytosis-lymphadenopathy plus syndrome is a rare autosomal recessive multisystem disorder caused by SLC29A3 mutations.Diagnosis relies on clinical, histopathological and genetic findings, and should be considered in patients with atypical combinations of cutaneous, endocrine and skeletal features.Multisystem involvement is associated with increased morbidity.