Phosphoglucomutase 1 deficiency misdiagnosed as Laron syndrome
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Seyit Ahmet Uçaktürk
,
Emre Özer
,
Ahmet Cevdet Ceylan
and
Eda Mengen
Abstract
Objectives
Protein glycosylation is a crucial process involving the addition of oligosaccharides to proteins, which plays a significant role in stabilizing proteins and mediating protein–protein interactions. Mutations in genes associated with glycosylation can lead to congenital disorders of glycosylation (CDG), resulting in multisystem disorders. One such example is phosphoglucomutase 1 (PGM1) -CDG, caused by a deficiency of the PGM1 enzyme. In this report, we describe a patient with PGM1-CDG who was initially misdiagnosed with growth hormone insensitivity and benefited from recombinant human insulin-like growth factor-1 (rhIGF-1) therapy.
Case Presentation
A 2-year-11-month-old female patient, born to first-degree cousin parents, presented with hypoglycemia and short stature. Her physical examination revealed frontal bossing, infantile facial appearance, and short stature. Laboratory investigations revealed that basal and stimulated growth hormone levels were very high, IGF-1 was low, and the inadequate response to the IGF generation test was consistent with growth hormone insensitivity (GHI). The patient was started on rhIGF-1 therapy, resulting in significant height gain. Subsequently, the patient showed improvement in height with rhIGF-1 therapy. The patient, who had additional findings such as elevated creatine kinase (CK) and transaminase levels and cardiomyopathy, was diagnosed with PGM1-CDG.
Conclusions
This case highlights that PGM1-CDG can mimic clinical and laboratory findings of GHI. CDG diagnosis should be considered in cases with clinical and laboratory findings of GHI accompanied by multisystem disorders such as hepatopathy, elevated CK, and cardiomyopathy. This patient’s successful response to rhIGF-1 therapy highlights the potential benefits of targeted therapies in treating growth hormone-related disorders in patients.
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Research ethics: As this is a case report, formal approval from an ethics committee was not required.
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Informed consent: Informed consent for publication of case details was obtained from the patient’s parents.
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Author contributions: Seyit Ahmet Uçaktürk, Eda Mengen: responsible for the patient’s medical care, literature search, interpreted the findings, agreed to the final version of the manuscript, and took full responsibility for the manuscript. Ahmet Cevdet Ceylan has conducted and interpreted genetic studies.
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Use of Large Language Models, AI and Machine Learning Tools: Not used.
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Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Research funding: The authors declared that this study received no financial support.
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Data availability: Data are available upon reasonable request.
References
1. de Zegher, F, Jaeken, J. Endocrinology of the carbohydrate-deficient glycoprotein syndrome type 1 from birth through adolescence. Pediatr Res 1995;37:395–401. https://doi.org/10.1203/00006450-199504000-00003.Search in Google Scholar PubMed
2. Jaeken, J. Congenital disorders of glycosylation: a multi-genetic disease family with multiple subcellular locations. J Mother Child 2020;24:14–20. https://doi.org/10.34763/jmotherandchild.20202402si.2005.000004.Search in Google Scholar PubMed PubMed Central
3. Altassan, R, Radenkovic, S, Edmondson, AC, Barone, R, Brasil, S, Cechova, A, et al.. International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): diagnosis, follow-up, and management. J Inherit Metab Dis 2021;44:148–63. https://doi.org/10.1002/jimd.12286.Search in Google Scholar PubMed PubMed Central
4. Savage, MO, Hwa, V, David, A, Rosenfeld, RG, Metherell, LA. Genetic defects in the growth Hormone-IGF-I axis causing growth hormone insensitivity and impaired linear growth. Front Endocrinol (Lausanne) 2011;2:95. https://doi.org/10.3389/fendo.2011.00095.Search in Google Scholar PubMed PubMed Central
5. Marquardt, T, Morava, E, Rust, S. Multiple phenotypes in phosphoglucomutase 1 deficiency. N Engl J Med 2014;370:2051. https://doi.org/10.1056/NEJMc1403446.Search in Google Scholar PubMed
6. Zeevaert, R, Scalais, E, Muino Mosquera, L, De Meirleir, L, De Beaufort, C, Witsch, M, et al.. PGM1 deficiency diagnosed during an endocrine work-up of low IGF-1 mediated growth failure. Acta Clin Belg 2016;71:435–7. https://doi.org/10.1080/17843286.2016.1142043.Search in Google Scholar PubMed
7. Collett-Solberg, PF, Cohen, P. The role of the insulin-like growth factor binding proteins and the IGFBP proteases in modulating IGF action. Endocrinol Metab Clin N Am 1996;25:591–614. https://doi.org/10.1016/s0889-8529(05)70342-x.Search in Google Scholar PubMed
8. Firth, SM, McDougall, F, McLachlan, AJ, Baxter, RC. Impaired blockade of insulin-like growth factor I (IGF-I)-induced hypoglycemia by IGF binding protein-3 analog with reduced ternary complex-forming ability. Endocrinology 2002;143:1669–76. https://doi.org/10.1210/endo.143.5.8764.Search in Google Scholar PubMed
9. Janosi, JB, Firth, SM, Bond, JJ, Baxter, RC, Delhanty, PJ. N-Linked glycosylation and sialylation of the acid-labile subunit. Role in complex formation with insulin-like growth factor (IGF)-binding protein-3 and the IGFs. J Biol Chem 1999;274:5292–8. https://doi.org/10.1074/jbc.274.9.5292.Search in Google Scholar PubMed
10. Philippou, A, Maridaki, M, Pneumaticos, S, Koutsilieris, M. The complexity of the IGF1 gene splicing, posttranslational modification and bioactivity. Mol Med 2014;20:202–14. https://doi.org/10.2119/molmed.2014.00011.Search in Google Scholar PubMed PubMed Central
11. Dricu, A, Carlberg, M, Wang, M, Larsson, O. Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res 1997;57:543–8.Search in Google Scholar
12. Siddals, KW, Marshman, E, Westwood, M, Gibson, JM. Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonic acid depletion: synergy between protein prenylation and receptor glycosylation pathways. J Biol Chem 2004;279:38353–9. https://doi.org/10.1074/jbc.m404838200.Search in Google Scholar PubMed
13. Di Patria, L, Annibalini, G, Morrone, A, Ferri, L, Saltarelli, R, Galluzzi, L, et al.. Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation. Cell Mol Life Sci 2022;79:150. https://doi.org/10.1007/s00018-022-04180-x.Search in Google Scholar PubMed PubMed Central
14. EMA. Increlex – summary of product characteristics; 2020. available from https://www.ema.europa.eu/en/documents/product-information/increlex-eparproduct-information_en.pdf.Search in Google Scholar
15. Miller, BS, Duffy, MM, Addo, OY, Sarafoglou, K. rhIGF-1 therapy for growth failure and IGF-1 deficiency in congenital disorder of glycosylation Ia (PMM2 deficiency). J Investig Med High Impact Case Rep 2013;1:2324709613503316. https://doi.org/10.1177/2324709613503316.Search in Google Scholar PubMed PubMed Central
16. Nolting, K, Park, JH, Tegtmeyer, LC, Zühlsdorf, A, Grüneberg, M, Rust, S, et al.. Limitations of galactose therapy in phosphoglucomutase 1 deficiency. Mol Genet Metab Rep 2017;13:33–40. https://doi.org/10.1016/j.ymgmr.2017.07.010.Search in Google Scholar PubMed PubMed Central
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