Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease.

The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)). To elucidate the molecular basis of FHC, we performed autozygosity mapping studies in a large consanguineous family and identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate genes within the target interval identified biallelic germline mutations in SLC29A3 in the FHC kindred and in two families reported to have familial RDD. Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread expression by e14.5 with prominent expression in the central nervous system, eye, inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3) with affinity for adenosine. Recently germline mutations in SLC29A3 were also described in two rare autosomal recessive disorders with overlapping phenotypes: (a) H syndrome (MIM 612391) that is characterised by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and hypogonadism; and (b) PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus) syndrome. Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new diagnostic category of SLC29A3 spectrum disorder.

Mesenchymal Hamartoma of the Liver in an Infant With Beckwith-Wiedemann Syndrome: A Rare Condition Mimicking Hepatoblastoma.

Patients with Beckwith-Wiedemann syndrome (BWS) are known to be at an increased risk for childhood malignancies, particularly Wilms tumor and hepatoblastoma. We report a case of genetically confirmed BWS in a 5-month-old girl who presented with a 9.5-cm abdominal mass associated with elevated α-fetoprotein levels. The clinical impression was strongly suggestive of hepatoblastoma. Histologic examination of the surgically excised mass revealed mesenchymal hamartoma of the liver (MHL), a benign hepatic neoplasm.

Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness.

Rosai-Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with this condition. We now report two brothers of consanguineous Palestinian parents, whose lymphadenopathy, lymph node histology, and polyclonal hypergammaglobulinemia indicated RDD. The presence of intrauterine fractures, short stature, and sensorineural hearing impairment suggested a rare familial form of the disorder. Moynihan et al. recently described a Pakistani family with a familial histiocytic disorder highly reminiscent of the brothers reported here, whose lymph node morphology was apparently consistent with RDD as well. The presence of sensorineural deafness, short stature, and joint contractures, however, suggested a separate, rare autosomal recessive syndrome referred to as Faisalabad histiocytosis, after the family's place of origin. We believe that the brothers described here represent a second family with Faisalabad histiocytosis, which mimics RDD histologically.