The clinical approach to child and adolescent patients with lipodystrophy: a series of international case discussions

Rebecca J Brown^1,2*Baris Akinci^3,4Saif Al Yaarubi⁵Elise Bismuth⁶Marco Cappa⁷Asma Deeb⁸Clemens Kamrath⁹Carla Musso¹⁰Nivedita Patni¹¹Flavia Prodam¹²Rachel Williams^13,14Martin Wabitsch^15,16

• ¹National Institute of Diabetes and Digestive and Kidney Diseases (NIH), Bethesda, Maryland, United States
• ²National Institutes of Health (NIH), Bethesda, Maryland, United States
• ³Dokuz Eylül University Health Campus Technopark (DEPARK), Dokuz Eylül University, Alsancak, İzmir, Türkiye
• ⁴Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir, Türkiye
• ⁵Pediatric Endocrinology, Oman Medical Specialty Board, Muscat, Oman
• ⁶Department of Pediatric Endocrinology, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Paris, France
• ⁷Research Unit for Innovative Therapies in Endocrinopathies, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
• ⁸Division of Paediatric Endocrine, Sheikh Shakhbout Medical City and College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
• ⁹Centre of Child and Adolescent Medicine, Department of General Pediatrics and Neonatology, University Hospital Freiburg, Freiburg, Germany
• ¹⁰Fundacion Favaloro Hospital Universitario, Buenos Aires, Buenos Aires, Argentina
• ¹¹Division of Pediatric Endocrinology, Department of Pediatrics, Medical School, University of Texas Southwestern Medical Center, Dallas, Texas, United States
• ¹²Unit of Endocrinology, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
• ¹³Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
• ¹⁴Nottingham Children's Hospital, Nottingham, United Kingdom
• ¹⁵German Center for Child and Adolescent Health (DZKJ), Ulm site, Ulm, Germany
• ¹⁶Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Hospital, Ulm, Germany

Introduction: Lipodystrophy syndromes comprise a group of rare endocrine disorders characterized by the generalized or partial loss of adipose tissue. Affected individuals frequently display absolute or relative reductions in leptin, a key adipokine regulator of hunger-satiety signaling, and are predisposed to a range of metabolic and end-organ complications, often from a young age. The presentation and severity of lipodystrophy syndromes is largely dependent on the extent of adipose tissue loss while comorbidities often deteriorate with age. In this regard, optimizing care for children and adolescents with lipodystrophy syndrome is a pivotal step in supporting them into adulthood. To assist clinicians with limited experience of managing young patients with lipodystrophy syndromes, we describe our clinical approach to a series of pediatric patients with this rare disease.Methods: The clinical history, diagnosis, disease management and follow-up care of 10 international pediatric patients with lipodystrophy syndromes are presented. Teaching points from each case study are also provided. Most of these cases are based on patients from our clinics with certain details changed to protect privacy. Others represent hypothetical scenarios based on our clinical experience supported by review of the medial literature and are included here for educational purposes. Results: Our patients illustrate the broad phenotypic spectrum of lipodystrophy syndromes that can manifest early in life. We highlight the importance of timely and accurate diagnosis in guiding early disease management strategies to help reduce the risk of comorbidities. The challenges faced by clinicians managing pediatric patients with lipodystrophy syndromes and how these challenges may differ from adult patients are also explored. Discussion: The cases presented in this manuscript may assist clinical teams to promptly diagnose and holistically manage young patients with lipodystrophy syndromes and help optimize clinical outcomes as they transition to adult care.