The SLC29A3 gene, encoding hENT3, a member of the equilibrative
nucleoside transporter family, has recently been found mutated in
Faisalabad histiocytosis, pigmented hypertrichotic
dermatosis with
insulin-dependent diabetes, familial
sinus histiocytosis with massive lymphadenopathy (SHML), and H syndromes. We here report clinical and genetic findings of an Egyptian family with H syndrome. We describe two siblings, a 19-yr old girl and a 15-yr old boy, of consanguineous parents. From 5 yr of age, the girl developed bilateral flexion
deformity of interphalengeal joints and
insulin-dependent diabetes mellitus. At age 7 yr, prominent hyperpigmented patches appeared on the skin at lower limbs, genitalia, and trunk. On clinical examination, she had hepatosplenomegaly, generalized
lymphadenopathy,
left ventricular hypertrophy,
sensorineural hearing loss,
hypogonadism, short stature, and characteristic dysmorphic features. Her brother had fixed flexion
contractures of the feet, profound
sensorineural hearing loss, characteristic dysmorphic features, but no diabetes. DNA sequence analysis revealed a homozygous mutation (c.300+1G>C) in SLC29A3 in both siblings. The phenotype and genotype of the siblings were compatible with that of the H syndrome, although the features were overlapping with those found in pigmented hypertrichotic
dermatosis with
insulin-dependent diabetes, familial SHML, and
Faisalabad histiocytosis, indicating that these four syndromes may be regarded as one disease with varying phenotypic features. A new, common name for these conditions is warranted.