Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: effects of metreleptin substitution
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Suleyman Cem Adiyaman
,
Julia v.Schnurbein
and
Clemens Kamrath
Abstract
Objectives
Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare autosomal recessive disorders characterized by near/total absence of body fat. Pathogenic variants in polymerase-I and transcript release factor gene (PTRF), or CAVIN1, is responsible for CGL4. In addition to generalized fat loss, patients with CGL4 were reported to suffer from myopathy, malignant cardiac arrhythmias, gastrointestinal disorders, and skeletal abnormalities. Here we describe the phenotype of a child with CGL4 due to a rare, novel pathogenic variant in the PTRF/CAVIN1 gene and the long-term effects of metreleptin substitution on comorbidities.
Case presentation
We describe a now 20-year-old female patient. At the age of 14-years, she was referred to the University Clinic because of uncontrolled diabetes with an HbA1c of 9.3%, requiring 2.4 IU insulin/kg total-body-weight to normalize blood glucose, hepatomegaly, and hypertriglyceridemia of 515 mg/dL. Additionally, she was suffering from malignant cardiac arrhythmia, myopathy, and hyperCKemia. In light of these clinical findings, she was diagnosed with CGL due to a rare, novel variant in the PTRF gene, and was started on metreleptin, a synthetic analog of human leptin. After the initiation of metreleptin treatment, insulin therapy could be stopped and improvement of sonographically assessed liver size was observed, even though serum liver function test stayed mildly elevated. Furthermore, a noticeable improvement of the serum triglyceride levels was also seen. Medical care and regular follow-up visits are being carried out by a multi-disciplinary team.
Conclusions
Although CGL4 is rare, due to its life-threatening comorbidities and the opportunity for an early intervention, it is important that the clinicians should recognise these patients.
Acknowledgments
We would like to thank the Society of Endocrinology and Metabolism of Turkey for supporting SCA with a scholarship at the Division of Pediatric Endocrinology and Diabetes University Medical Center, Ulm, Germany.
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Research funding: Not applicable.
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Author contribution: S.C.A., M.W., and C.K. wrote the initial draft. All authors read and approved the final manuscript.
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Competing interests: The authors have no conflicts of interest to disclose.
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Informed consent: Informed consent for publication was signed by the patient and her parents.
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Ethics approval: Ethics approval was not required as the patient was not involved in a clinical study.
References
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Articles in the same Issue
- Frontmatter
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- Influence of the SARS-CoV-2 pandemic on paediatric patients with type 1 diabetes mellitus after one year of follow-up
- Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls
- Differences in the proportion of Croatian adolescents with abnormal individual metabolic syndrome components adjusted to gender and different criterion for individual metabolic syndrome component
- Low HDL-C is a non-fasting marker of insulin resistance in children
- Impact of COVID-19 lockdown on idiopathic central precocious puberty – experience from an Indian centre
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- Urinary phthalate concentrations are associated with total fat mass in Thai children
- Clinical profile and aetiologies of delayed puberty: a 15 years’ experience from a tertiary centre in Sudan
- Case Reports
- Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: effects of metreleptin substitution
- Prepubertal and pubertal gonadal morphology, expression of cell lineage markers and hormonal evaluation in two 46,XY siblings with 17β-hydroxysteroid dehydrogenase 3 deficiency
- Pleomorphism of the HPG axis with NR0B1 gene mutation — a case report of longitudinal follow-up of a proband with central precocious puberty
- Successful treatment of severe hypertriglyceridemia with icosapent ethyl in a case of congenital generalized lipodystrophy type 4
Articles in the same Issue
- Frontmatter
- Original Articles
- The effects of topical iodine containing antiseptics on thyroidal status and early neurodevelopment of preterm infants
- Effect of COVID-19 pandemic on presentation and referral patterns of newly diagnosed children with type 1 diabetes in a developing country
- Influence of the SARS-CoV-2 pandemic on paediatric patients with type 1 diabetes mellitus after one year of follow-up
- Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls
- Differences in the proportion of Croatian adolescents with abnormal individual metabolic syndrome components adjusted to gender and different criterion for individual metabolic syndrome component
- Low HDL-C is a non-fasting marker of insulin resistance in children
- Impact of COVID-19 lockdown on idiopathic central precocious puberty – experience from an Indian centre
- The relationship between metabolic syndrome and bone mineral density in adolescents: analysis of the National Health and Nutrition Examination Survey
- Long-term follow-up of alkaptonuria patients: single center experience
- Local aromatase excess with recruitment of unusual promoters of CYP19A1 gene in prepubertal patients with gynecomastia
- Urinary phthalate concentrations are associated with total fat mass in Thai children
- Clinical profile and aetiologies of delayed puberty: a 15 years’ experience from a tertiary centre in Sudan
- Case Reports
- Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: effects of metreleptin substitution
- Prepubertal and pubertal gonadal morphology, expression of cell lineage markers and hormonal evaluation in two 46,XY siblings with 17β-hydroxysteroid dehydrogenase 3 deficiency
- Pleomorphism of the HPG axis with NR0B1 gene mutation — a case report of longitudinal follow-up of a proband with central precocious puberty
- Successful treatment of severe hypertriglyceridemia with icosapent ethyl in a case of congenital generalized lipodystrophy type 4
