ESPE Abstracts

Background: FPLD2 results from autosomal dominant mutations in the LMNA gene. The physical appearance develops through adolescence where subcutaneous fat deposits of the limbs, trunk, buttocks and legs do not develop resulting in a muscular appearance. The metabolic phenotype includes elevations in triglyceride concentrations and hepatosteatosis with resultant insulin resistance. Co-morbidities that may manifest during young adulthood include early-onset diabetes, coronary artery disease and hypertrophic cardiomyopathy, with resultant reduction in life expectancy. The most effective management is the adoption of a lifelong low fat diet to minimise ectopic fat accumulation. Conventional therapies for hypertriglyceridaemia and diabetes have limited efficacy. Recombinant leptin can be beneficial and has recently been approved for use in patients with FPLD2 who have diabetes and elevated triglycerides. Genetic testing permits the diagnosis of FPLD2 in the offspring of index cases before they would present clinically. Current guidance is that they should follow a healthy low fat diet, with annual screening for co-morbidities, however the natural history of FPLD2 throughout childhood is not well understood. We report outcomes from a cohort of children with FPLD2 under the care of the UK National Centre for severe insulin resistance in Cambridge, United Kingdom. Patients are offered an annual appointment for clinician and dietetic review with screening for co-morbidities.

Methods: Following institutional approval, a retrospective case note review of 12 [5M] children with FPLD2 was undertaken. Relationships between dependent variables (HbA1c, triglycerides, fasting insulin, fasting glucose and ALT) across time were explored using a multivariate model, adjusted for age and gender.

Results: Age median [range] at first appointment was 9.8[6.0-14.6]yrs with no gender difference. Age at most recent follow up was 16.3 [9.1-21.3]yrs with 4.2[1.0-6.0]yrs follow up. 3 patients (all female) developed diabetes between 12 and 19yrs. 1 female has hypertrophic cardiomyopathy and 4 [1M] developed mild hepatic steatosis by a median age of 14[12-15]yrs. 3 patients [1M] reported mental health problems related to lipodystrophy. There were no relationships between biochemical results and age.

Conclusion: In this small cohort of children, despite dietetic input, we found evidence of co-morbidities after the age of 12 years, more commonly in females, consistent with described outcomes for adults. The absence of relationships with biochemical screening tests and age likely reflects the small numbers in this cohort. We propose that, whilst clinical review and dietetic advice and support are of benefit for children with FPLD2, undertaking formal screening for co-morbidities before the age of 10 years is unlikely to be of benefit, however clinical input from an MDT including dietician, psychologist and clinician should be offered from diagnosis.