Endocrine Abstracts

Background: The H-syndrome is a recently described very rare monogenic systemic autoinflammatory autosomal-recessive genodermatosis with young onset of diabetes without evidence of autoimmunity. It is caused by mutations in the SLC29A3 gene, which encodes the equilibrative nucleoside transporter hENT3.

Objectives: To study the clinical features and confirm the genetic diagnosis in a subject with young onset of diabetes.

Subject and methods: Utilizing next generation sequencing we carried out mutational analysis of SLC29A3 gene in the chr.10q22.1 and selectively investigated this patient for various other features of this genodermatosis.

Case report and discussion: A 20-year-old lady, born to parents of non-consanguineous marriage developed diabetes at the age of 6 years, with ketosis at onset. She required Insulin from the time of diagnosis. Subsequently she noticed progressively increasing hyperpigmented lesions over the trunk and lower limbs and excess hair growth. On examination she had symmetrical large hyperpigmented indurated plaques and hypertrichosis over the lower limbs with sparing of the face. The characteristic skin lesions led to the suspicion of a genodermatosis, namely the H-syndrome and elevated inflammatory markers (CRP and ESR) further added to the clue. The next generation sequencing of SLC29A3 gene was done in our molecular lab, revealed a homozygous mutation c.400C>T, p.R134C, which was confirmed by Sanger sequencing. The term ‘H-syndrome’ refers to systemic features starting with letter ‘H’ – hyperpigmentation, hypertrichosis, hyperglycemia, hypogonadism, hypothyroidism, heart anomalies (bicuspid aortic valve), hearing loss, and low height which were present. Clinodactyly, icthyiosis and arthrogryposis of the ankle were peculiar to our subject.

Conclusions: Young onset of diabetes with the dermatological phenotype of pigmentary hypertrichosis, followed by appropriate biochemical and genetic analysis led to the diagnosis of H-syndrome. Genetic testing confirms the diagnosis and would be useful in further counseling.