H Syndrome: A Rare Monogenic Cause of Insulin-Dependent Diabetes Mellitus

Introduction:

H syndrome (HS) is an autosomal recessive multisystemic disorder, named after the first letter of the characteristic clinical features of hyperpigmentation, hypertrichosis, hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, low height (short stature), hyperglycemia/diabetes mellitus (DM), and hallux valgus/flexion contractures. Causative mutations have been identified in the SLC29A3 gene encoding the human equilibrative nucleoside transporter 3 (hENT3), which is thought to serve as a transporter of nucleosides from the inside of the late endosome/lysosomes to the cytoplasm and also across the inner mitochondrial membrane.

Case:

A seven-year-old boy, with insulin-dependent DM (IDDM) diagnosed at 18 months of age, developed bilateral cervical masses at the age of 6 years. His height was 120.4 cm [-0.2 standard deviation (SD)] and weight was 25 kg (0.5 SD). He had coarse face, depressed nasal bridge, hypermetropia, right esotropia, cervical lymphadenopathy (LAP), and multiple nevi at various sites of the body. The laboratory evaluation for LAP revealed normal results with regard to hematologic and serologic tests except the presence of AntiSLC70 antibodies. Excisional lymph node biopsy demonstrated massive sinus dilatation, histiocyte proliferation which was stained with S100 and CD68, capsular and pericapsular fibrosis in the adipose tissue and emperipolesis, consistent with Rosai-Dorfman disease. Both LAP and DM suggested the presence of HS. Because of the combination of two known but relatively rare manifestations of HS genetic analysis of the SLC29A3 gene was carried out and revealed a novel homozygous mutation of p.367A>T; (c.1099G>A).

Discussion:

HS is a genetic dermatologic disease with different manifestations. Early-onset IDDM may even be the first manifestation of H syndrome as in our case, presenting a diagnostic challenge. Diabetic patients with cutaneous signs or histiocytic LAP should be investigated for HS.