Home Short stature in a boy with atypical progeria syndrome due to LMNA c.433G>A [p.(Glu145Lys)]: apparent growth hormone deficiency but poor response to growth hormone therapy
Article
Licensed
Unlicensed Requires Authentication

Short stature in a boy with atypical progeria syndrome due to LMNA c.433G>A [p.(Glu145Lys)]: apparent growth hormone deficiency but poor response to growth hormone therapy

  • Ledjona Toni EMAIL logo , Petra Dušátková , Dana Novotná , Daniela Zemková , Štěpánka Průhová and Jan Lebl
Published/Copyright: June 13, 2019
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 32 Issue 7

Abstract

Background

Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by pathogenic variants in the LMNA gene, which leads to premature aging. The median life expectancy is shortened to 13 years due to cardiovascular complications.

Case report

We present a boy born with a pathogenic LMNA variant c.433G > A, which causes atypical progeria syndrome (APS) and was previously described in one single patient. When investigated for poor growth prior to the diagnosis of APS, his laboratory tests revealed growth hormone (GH) deficiency and magnetic resonance imaging (MRI) of the midbrain showed partial empty sella. GH treatment had only a limited and transient effect. His first ischemic complication manifested at age 4.2 years; at the age of 7 years, he had a fatal haemorrhagic stroke.

Conclusion

To the best of our knowledge, this is the first patient with APS showing partial empty sella and GH deficiency that might have contributed to his poor growth. GH failed to improve long-term outcome.

Keywords: atypical progeria syndrome; growth hormone deficiency; LMNA
Corresponding author: Ledjona Toni, MD, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, Prague 5, 150 06, Praha, Czech Republic, Phone: +420 224 432 001, Fax: +420 224 432 020

Acknowledgments

This work was supported by a grant from AZV of Czech Ministry of Health No. 18-07-00283. We would like to thank our case patient’s parents for their cooperation and providing consent for the publication of the pictures above.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by a grant from AZV of Czech Ministry of Health No. 18-07-00283.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Progeria Research Foundation (PRF) webpage. Available at: https://www.progeriaresearch.org/. Accessed 17 Feb 2019.Search in Google Scholar

2. DeBusk FL. The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J Pediatr 1972;80:697–724.10.1016/S0022-3476(72)80229-4Search in Google Scholar

3. Hennekam RC. Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet A 2006;140:2603–24.10.1002/ajmg.a.31346Search in Google Scholar PubMed

4. Goldman RD, Gruenbaum Y, Moir RD, Shumaker DK, Spann TP. Nuclear lamins: building blocks of nuclear architecture. Genes Dev 2002;16:533–47.10.1101/gad.960502Search in Google Scholar PubMed

5. De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, et al. Lamin a truncation in Hutchinson-Gilford progeria. Science 2003;300:2055.10.1126/science.1084125Search in Google Scholar PubMed

6. Garg A, Subramanyam L, Agarwal AK, Simha V, Levine B, et al. Atypical progeroid syndrome due to heterozygous missense LMNA mutations. J Clin Endocrinol Metab 2009;94:4971–83.10.1210/jc.2009-0472Search in Google Scholar PubMed PubMed Central

7. Doubaj Y, De Sandre-Giovannoli A, Vera EV, Navarro CL, Elalaoui SC, et al. An inherited LMNA gene mutation in atypical progeria syndrome. Am J Med Genet Part A 2012;158A:2881–7.10.1002/ajmg.a.35557Search in Google Scholar PubMed

8. Barthelemy F, Navarro C, Fayek R, Da Silva N, Roll P, et al. Truncated prelamin A expression in HGPS-like patients: a transcriptional study. Eur J Hum Genet 2015;23:1051–61.10.1038/ejhg.2014.239Search in Google Scholar PubMed PubMed Central

9. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 2003;423:293–8.10.1038/nature01629Search in Google Scholar PubMed

10. Taimen P, Pfleghaar K, Shimi T, Moller D, Ben-Harush K, et al. A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization. Proc Natl Acad Sci USA 2009;106:20788–93.10.1073/pnas.0911895106Search in Google Scholar PubMed PubMed Central

11. Kaufmann A, Heinemann F, Radmacher M, Stick R. Amphibian oocyte nuclei expressing lamin A with the progeria mutation E145K exhibit an increased elastic modulus. Nucleus 2011;2:310–19.10.4161/nucl.2.4.16119Search in Google Scholar PubMed

12. Apte K, Stick R, Radmacher M. Mechanics in human fibroblasts and progeria: lamin A mutation E145K results in stiffening of nuclei. J Mol Recognit 2016;30:1–11.10.1002/jmr.2580Search in Google Scholar

13. Smith AS, Wiznitzer M, Karaman BA, Horwitz SJ, Lanzieri CF. MRA detection of vascular occlusion in a child with progeria. Am J Neuroradiol 1993;14:441–3.Search in Google Scholar

14. Abdenur J, Brown WT, Friedman S, Smith M, Lifshitz F. Response to nutritional and growth hormone treatment in progeria. Metabolism 1997;46:851–6.10.1016/S0026-0495(97)90069-XSearch in Google Scholar

15. Sadeghi-Nejad A, Demmer L. Growth hormone therapy in progeria. J Pediatr Endocrinol Metab 2007;20:633–7.10.1515/JPEM.2007.20.5.633Search in Google Scholar

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2019-0107).

Received: 2019-02-28
Accepted: 2019-03-31
Published Online: 2019-06-13
Published in Print: 2019-07-26

© 2019 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Effect of safflower yellow on early type II diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials
  4. Original Articles
  5. Genomic study via chromosomal microarray analysis in a group of Romanian patients with obesity and developmental disability/intellectual disability
  6. Clinical and molecular characteristics and time of diagnosis of patients with classical galactosemia in an unscreened population in Turkey
  7. Assessment of retinal thickness as a marker of brain masculinization in children with congenital adrenal hyperplasia: a pilot study
  8. Auditory event-related potentials demonstrate early cognitive impairment in children with subclinical hypothyroidism
  9. Cardiovascular risk factors in children with type 1 diabetes mellitus
  10. The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents
  11. The metabolic consequences of overweight in a cohort of children with type 1 diabetes
  12. The spectrum of pediatric adrenal insufficiency: insights from 34 years of experience
  13. Growth screening in children aged 3–5 years: a useful tool for public health programs in community pediatrics
  14. Selective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy patients
  15. Determinants for low bone mineral density in pre-school children: a matched case-control study in Wuhan, China
  16. Genetic polymorphisms associated with obesity and non-alcoholic fatty liver disease in Asian Indian adolescents
  17. Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes
  18. Severe, persistent neonatal hypoglycemia as a presenting feature in patients with congenital hypopituitarism: a review of our case series
  19. Case Reports
  20. Short stature in a boy with atypical progeria syndrome due to LMNA c.433G>A [p.(Glu145Lys)]: apparent growth hormone deficiency but poor response to growth hormone therapy
  21. A novel mutation leading to the lethal form of carnitine palmitoyltransferase type-2 deficiency
  22. Diagnosis of cyclic Cushing’s disease manifests as early morning hyperglycemia in a patient with previously well-controlled type 1 diabetes
  23. Short Communication
  24. Replacement of breastfeeding with medical food for the treatment of galactosemia and phenylketonuria: maternal stress
https://doi.org/10.1515/jpem-2019-0107
Keywords for this article
atypical progeria syndrome; growth hormone deficiency; LMNA

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Effect of safflower yellow on early type II diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials
  4. Original Articles
  5. Genomic study via chromosomal microarray analysis in a group of Romanian patients with obesity and developmental disability/intellectual disability
  6. Clinical and molecular characteristics and time of diagnosis of patients with classical galactosemia in an unscreened population in Turkey
  7. Assessment of retinal thickness as a marker of brain masculinization in children with congenital adrenal hyperplasia: a pilot study
  8. Auditory event-related potentials demonstrate early cognitive impairment in children with subclinical hypothyroidism
  9. Cardiovascular risk factors in children with type 1 diabetes mellitus
  10. The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents
  11. The metabolic consequences of overweight in a cohort of children with type 1 diabetes
  12. The spectrum of pediatric adrenal insufficiency: insights from 34 years of experience
  13. Growth screening in children aged 3–5 years: a useful tool for public health programs in community pediatrics
  14. Selective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy patients
  15. Determinants for low bone mineral density in pre-school children: a matched case-control study in Wuhan, China
  16. Genetic polymorphisms associated with obesity and non-alcoholic fatty liver disease in Asian Indian adolescents
  17. Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes
  18. Severe, persistent neonatal hypoglycemia as a presenting feature in patients with congenital hypopituitarism: a review of our case series
  19. Case Reports
  20. Short stature in a boy with atypical progeria syndrome due to LMNA c.433G>A [p.(Glu145Lys)]: apparent growth hormone deficiency but poor response to growth hormone therapy
  21. A novel mutation leading to the lethal form of carnitine palmitoyltransferase type-2 deficiency
  22. Diagnosis of cyclic Cushing’s disease manifests as early morning hyperglycemia in a patient with previously well-controlled type 1 diabetes
  23. Short Communication
  24. Replacement of breastfeeding with medical food for the treatment of galactosemia and phenylketonuria: maternal stress
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 10.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2019-0107/html
Scroll to top button