A Case of H Syndrome Showing Immunophenotye Similarities to Rosai–Dorfman Disease

Abstract

H syndrome (OMIM 612391) is a recently described autosomal recessive genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin and systemic manifestations including hepatosplenomegaly, cardiac anomalies, hearing loss, hypogonadism, low height, hypertriglyceridemia, hallux valgus, and flexion contractures. H syndrome results from mutations in the SLC29A3 gene, which encodes the human equilibrative nucleoside transporter hENT3. The cutaneous histopathology is characterized by a striking mononuclear cell infiltrate in the dermis consisting of CD68+ monocyte-derived cells and CD34+ and factor XIIIa+ dendrocytes. We describe a case of H syndrome in which the infiltrating mononuclear cells were CD68+, CD163+, S-100+, and CD1a-, thus simulating the immunophenotype observed in Rosai-Dorfman disease (RDD). The immunostaining for CD21, fascin, and CD34 were negative, and there were also many factor XIIIa+ dendrocytes interspersed within the dense mononuclear cell infiltrate. Recent findings of biallelic mutations in SLC29A3 in 2 families reported to have familial RDD and in a kindred with Faisalabad histiocytosis (OMIM 602782), which is an autosomal inherited form of histiocytosis with similarities to RDD, may explain the RDD-like immunophenotype in our H syndrome case.

The histopathology and phenotypic variability in H syndrome

“…The cutaneous findings and histopathology were consistent with H syndrome 4, 5. Molecular studies performed on peripheral blood revealed a recurrent mutation c.G1309>A, which is expected to lead to glycine‐to‐arginine substitution in hENT3 (p.Gly437Arg) 1, 3, 6.…”

“…Associated systemic manifestations include hepatosplenomegaly, congenital cardiac anomalies, hearing loss, hypogonadism, short stature, and hyperglycemia. H syndrome is caused by mutations in the gene SLC29A3 which encodes hENT3, a member of the human equilibrative nucleoside transporter family 1, 2, 3, 4, 5.…”

“…The histiocytes display immunophenotypic similarity to Rosai–Dorfman disease (RDD), that is, CD68+, CD163+, S100+, and negative CD1a 4. Colmenero et al 5 recently detected emperipolesis in addition to the RDD‐like phenotype.…”

A Case of SLC29A3 Spectrum Disorder—Unresponsive to Multiple Immunomodulatory Therapies

“…Our case describes the abnormal immunological findings that may be present in SLC29A3 spectrum disorders. This has rarely been explicitly reported despite the observation that autoimmune conditions such as haemolytic anaemia [3,4] and pancytopenia [5] may be associated with the syndrome. To date we could only find three other cases which characterized the immune system in affected patients.…”

“…They are all caused by homozygous or compound heterozygous mutation in the SLC29A3 gene on chromosome 10q22, hence they are also called SLC29A3 spectrum disorders (1)(2)(3)(4)(5)(6). Their clinical features are summarised in Figure 1.…”