Current Diagnosis, Treatment and Clinical Challenges in the Management of Lipodystrophy Syndromes in Children and Young People

Abstract

Lipodystrophy is a heterogeneous group of disorders characterized by lack of body fat in characteristic patterns, which can be genetic or acquired. Lipodystrophy is associated with insulin resistance that can develop in childhood and adolescence, and usually leads to severe metabolic complications. Diabetes mellitus, hypertriglyceridemia, and hepatic steatosis ordinarily develop in these patients, and most girls suffer from menstrual abnormalities. Severe complications develop at a relatively young age, which include episodes of acute pancreatitis, renal failure, cirrhosis, and complex cardiovascular diseases, and all of these are associated with serious morbidity. Treatment of lipodystrophy consists of medical nutritional therapy, exercise, and the use of anti-hyperglycemic and lipid-lowering agents. New treatment modalities, such as metreleptin replacement, promise much in the treatment of metabolic abnormalities secondary to lipodystrophy. Current challenges in the management of lipodystrophy in children and adolescents include, but are not limited to: (1) establishing specialized centers with experience in providing care for lipodystrophy presenting in childhood and adolescence; (2) optimizing algorithms that can provide some guidance for the use of standard and novel therapies to ensure adequate metabolic control and to prevent complications; (3) educating patients and their parents about lipodystrophy management; (4) improving patient adherence to chronic therapies; (5) reducing barriers to access to novel treatments; and (5) improving the quality of life of these patients and their families.

Approach to Diagnosing a Pediatric Patient With Severe Insulin Resistance in Low- or Middle-income Countries

“…In a subgroup of 17 patients who underwent liver biopsies, the histologic NAFLD activity score decreased, which could indicate that metreleptin could help prevent worsening of NAFLD to liver cirrhosis. Moreover, after 1 year of metreleptin treatment, the proportion of patients requiring insulin dropped from 45% to 23%, suggesting an improvement of insulin sensitivity ( 67 ). Metreleptin is well tolerated and side effects include injection site reactions, hypoglycemia, and development of neutralizing antibodies to metreleptin.…”

Treatment Options for Lipodystrophy in Children

“…However, this condition can be linked to physical concern, underlying disease mechanisms or both ( 21 ). Therefore, patients who aspire to a better cosmetic appearance may consider having cosmetic surgery ( 22 ). Excess unwanted localized fat tissue can be surgically excised or removed by liposuction ( 23 ).…”

“…Every dose adjustment must be maintained for at least 4 weeks and metabolic progression must be observed ( 19 ). Definitely, metreleptin doses should be adjusted every 3-6 months according to tolerability issues, metabolic parameters and weight change ( 22 ). Occasionally, a reduced metreleptin efficacy could derive from a non- adherence to the prescribed regimen.…”

Perilipin-1 autoantibodies linked to idiopathic lipodystrophy in the setting of two distinct breaks in immune tolerance

“…1 The excessive loss of adipocytes can lead to clinically severe outcomes including insulin resistance from lipolysis, metabolic abnormalities (diabetes mellitus and dyslipidemia) or even death. [1][2][3] Lipodystrophy is diagnosed largely by clinical phenotype but heterogeneous presentation, clinical mimicry and frequent association with complex disorders necessitates biomarkers.…”

“…Mutations in several lipid-droplet associated genes explain a genetic etiology for a subset of lipodystrophies; however, the acquired lipodystrophy subtype is largely idiopathic and biomarkers are lacking. [2][3] Frequent co-occurrence of acquired lipodystrophy with autoimmune disease has fueled suspicion of immune-mediated pathology. [4][5][6] We hypothesized that autoimmune associated acquired lipodystrophy may be associated with a common autoantibody that is adipocyte-specific.…”