Endocrine Abstracts

JOINT3451

Introduction: Homozygous familial hypercholesterolemia is a rare condition, with an estimated prevalence of 1 in 1 million individuals. Cases in multiple pregnancies have been scarcely reported in the literature.

Case Report: We report the case of a 15-year-old boy with no prior history of hypercholesterolemia, hospitalized for acute coronary syndrome. He was born to parents in a second-degree consanguineous marriage. He has three 12-year-old sisters from a trizygotic trichorionic multiple pregnancy. On examination, he presented with tendinous xanthomas, planar xanthomas, xanthelasma, and gerontoxon. Laboratory tests revealed severe hypercholesterolemia, with an LDL cholesterol level of 23 mmol/L. The Dutch Lipid Clinic Network criteria confirmed a diagnosis of definite familial hypercholesterolemia. Family screening identified hypercholesterolemia in several relatives, including one sister with a clinical and biological profile similar to the patient’s. The other two sisters from the triplet pregnancy also had hypercholesterolemia, though at less severe levels. Genetic analysis within the family revealed a severe LDL receptor gene mutation in the homozygous form in the patient and his similarly affected sister. The same mutation was found in a heterozygous form in the parents and the other two sisters. LDL apheresis was recommended for the homozygous patient and his affected sister, while the rest of the family was started on statins and ezetimibe.

Discussion: Homozygous familial hypercholesterolemia leads to early-onset atherosclerosis and premature death, often in the second decade of life. The LDL receptor gene mutation identified in our patients is classified as severe, with homozygous individuals retaining less than 2% of functional LDL receptors. While novel therapies may offer promising results, their high cost limits accessibility in our country. In our setting, LDL apheresis remains the only feasible and effective treatment. This case is exceptional due to the presence of familial hypercholesterolemia in triplet sisters from a multiple pregnancy. The different genotypes observed among the sisters are explained by the trizygotic trichorionic nature of the pregnancy, with one sister being homozygous and the other two heterozygous.