Hutchinson – gilford progeria syndrome – a portuguese rare case

Diana Catarino; Margarida Bastos; Cristina Ribeiro; Lucia Fadiga; Diana Silva; Joana Guiomar; Mariana Lavrador; Inês Vieira; Cátia Araújo; Bárbara Araújo; Isabel Dinis; Alice Mirante; Isabel Paiva

doi:10.1530/endoabs.70.AEP817

Introduction: Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare disease (1:4 million) characterized by a fatal premature aging. There are 162 cases worldwide, five of them in Portugal. It is caused by a sporadic autosomal dominant mutation in LMNA gene that encodes an abnormal variant of the laminin-A protein, named progerin. Although most babies born looking healthy, they begin to display some characteristics of Progeria around 18–24 months of life. The earliest signs are tightness of the skin, growth failure and loss of body fat and hair. Other signs include orthopaedic, ophthalmologic and cardiovascular disease. Without Progeria-specific treatment, children die of atherosclerosis (heart disease or stroke) at an average age of 14.5 years. The intellect of children is unaffected. Pathophysiology maintains unclear. The ‘Progeria Research Foundation’ funds research to find new treatmentsfor Progeria. There is currently no cure for Progeria.

Case report: 21-years female with HGPS caused by an 1824 C > T mutation in the exon 11 of LMNA gene. No family history of HGPS. First signs of disease at 4.5 months. Personal history of multiple fractures and dislocation of inferior members, hypermetropy, arterial hypertension, cardiac valvular disease, left ventricular hypertrophy, hypertriglyceridemia, hyperuricemia, palmar warts, subclinical hypothyroidism, multinodular goiter and secondary amenorrhea since 18 years. She is regularly monitored by orthopaedist, ophthalmologist, cardiologist, dermatologist, endocrinologist and gynaecologist. She maintains regularly follow-up at the Boston Children’s Hospital and takes part of a clinical trial with Lonafarnib – a farnesyltransferase inhibitor. She is followed up in an Endocrinology-Transition consultation since the age of 18, after initial follow-up at the Pediatric Hospital, for unmedicated subclinical hypothyroidism and multinodular goiter with infracentimetric cystic nodules. At the last evaluation, patient maintains subclinical hypothyroidism (negative autoimmunity) with no need of medication, medicated hypertriglyceridemia and prediabetes. Cranioencephalic MRI was normal.

Discussion and conclusion: The clinical case intends to demonstrate the rarity of this syndrome that is associated with multiple pathologies/comorbidities, needing regular monitorization throughout the life, by a multidisciplinary team, including medical and surgical teams. Due to the rarity of the disease, research and development of effective therapies becomes more difficult. The main of drugs currently available is reducing complications of the syndrome. Supportive therapy is also extremely relevant as it improves patients’ quality of life. Patient associations and international exchanges have been shown to be fundamental for families. https://www.progeriaresearch.org/

Endocrine Abstracts

AEP817