Describing the natural history of clinical, biochemical and radiological outcomes of children with familial partial lipodystrophy type 2 (FPLD2) from the UK: a retrospective case series.

Abstract

CONTEXT: Familial partial lipodystrophy type 2 (FPLD2) results from autosomal dominant mutations in the LMNA gene, causing lack of subcutaneous fat deposition and excess ectopic fat accumulation, leading to metabolic complications and reduced life expectancy. The rarity of the condition means that the natural history of FPLD2 throughout childhood is not well understood. We report outcomes in a cohort of 12 [5M] children with a genetic diagnosis of FPLD2, under the care of the UK National Severe Insulin Resistance Service [NSIRS] which offers multidisciplinary input including dietetic, in addition to screening for co-morbidities. OBJECTIVE: To describe the natural history of clinical, biochemical, and radiological outcomes of children with FPLD2. DESIGN: A retrospective case note review of children with a genetic diagnosis of FPLD2 who had been seen in the paediatric NSIRS was performed. PATIENTS: 12 [5M] individuals diagnosed with FPLD2 via genetic testing before age 18 and who attended the NSIRS clinic were included. MEASUREMENTS: Relationships between metabolic variables (HbA1c, triglycerides, fasting insulin, fasting glucose and ALT) across time, from first visit, to most recent, were explored using a multivariate model, adjusted for age and gender. Age of development of co-morbidities was recorded. RESULTS: 3 patients (all female) developed diabetes between 12 and 19yrs and were treated with Metformin. 1 female has hypertrophic cardiomyopathy and 4 [1M] patients developed mild hepatic steatosis at a median [range] age of 14[12-15]yrs. 3 [1M] patients reported mental health problems related to lipodystrophy. There were no relationships between biochemical results and age. Patients with diabetes had higher concentrations of ALT than patients who did not have diabetes, adjusted for age, gender and BMI SDS. CONCLUSIONS: Despite dietetic input, some patients, more commonly females, developed co-morbidities after the age of 10. The absence of relationships with biochemical results and age likely reflects the small cohort size. We propose that, whilst clinical review and dietetic support are beneficial for children with FPLD2, formal screening for co-morbidities before age 10 may not be of benefit. Clinical input from an MDT including dietician, psychologist, and clinician should be offered from diagnosis. This article is protected by copyright. All rights reserved.