Wed, Jun 4, 2025
Volume 18, Issue 5 (Sep-Oct 2024)
mljgoums 2024, 18(5): 12-13 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Ansari Q, Jain A, Randad K, Singh V, Sarkate A. Infantile presentation of osteoporosis-pseudoglioma syndrome: A Case Report. mljgoums 2024; 18 (5) :12-13
URL: http://mlj.goums.ac.ir/article-1-1733-en.html
URL: http://mlj.goums.ac.ir/article-1-1733-en.html
1- Department of Pediatrics, TNMC and BYL Nair Hospital, Mumbai, India , ansari.qudsiya31@gmail.com
2- Department of Pediatrics, TNMC and BYL Nair Hospital, Mumbai, India
2- Department of Pediatrics, TNMC and BYL Nair Hospital, Mumbai, India
Full-Text [PDF 334 kb]
(271 Downloads)
| Abstract (HTML) (931 Views)
Discussion
Osteoporosis-pseudoglioma syndrome due to mutations in LRP5 gene. LRP5 is a co-receptor of the Wnt signaling pathway and is situated in the osteoblast membrane between two other receptors, Frizzled 4 and Kremen. The Wnt pathway is involved in cell proliferation, adhesion, migration, and other activities. The binding of Frizzled 4 and LRP5 to Wnt stabilizes beta-catenin and activates bone formation (4,5). LRP5 regulates bone mineral density and is important for maintaining skeletal homeostasis; therefore, this disease presents with osteoporosis. Primary osteoporosis is seen in children with a heterozygous variant of LRP5 mutation (6). OPPG is characterized by osteoporosis and eye abnormalities that lead to vision loss. Ophthalmic findings vary from phthisis bulbi to less severe vitreoretinal findings, such as persistent hyperplasia of the primary vitreous (PHPV), congenital retinal folds, and exudative retinopathy. Fractures are more commonly seen after two years of life (7). Eye examination, coupled with bone phenotype and research of LRP5 mutation, are key points for diagnosing OPPG. It is an autosomal recessive condition each parent carries one copy of the mutated gene, and is asymptomatic for the condition; however, some carriers may have decreased bone mineral density. Bisphosphonates allow fracture prevention, improvement in bone mineral density, and enhanced mobility in children with OPPG (8). For children and adolescents diagnosed with OPPG who do not respond to other conventional therapies, short courses of teriparatide therapy may be helpful (9). New drugs favoring osteoblast function and osteoclast inhibition are potential candidates in the treatment of OPPG (10).
Conclusion
The clinician should differentiate OPPG from osteogenesis imperfecta and child abuse. This case portrays a rare presentation of OPPG syndrome, as the child presented with multiple fractures in infancy itself, the disease process was exaggerated due to the underlying metabolic bone disease, and the child did not have any ophthalmic findings which are generally diagnosed in infancy. The child is currently appropriate for corrected gestational age and follows objects. Close ophthalmic follow-up has been advised.
Acknowledgement
The authors thank the Dean, Topiwala National Medical College and BYL Nair Hospital for giving the opportunity to publish this manuscript.
Funding sources
Nil.
Ethical statement
The authors certify that they have obtained all appropriate patients’ parent consent.
Conflicts of interest
There are no conflicts of interest.
Author contributions
All the authors have read and approved the final version of the manuscript and agree to be accountable for the content presented.
Full-Text: (148 Views)
Introduction
Osteoporosis-pseudoglioma syndrome is a disorder caused by a mutation in the LRP5 (LDL receptor protein receptor 5) gene, located on chromosome 11q13.4 (1). Osteoporosis leads to bone deformities and fractures. With a typical history of minimal trauma, the time of onset and severity of the osteoporosis is highly variable (2). As the osteopaenic process stabilizes with age, prophylaxis and specialist care for fractures and deformities are essential to prevent incapacitating long-term problems. Intravenous bisphosphonate therapy may prevent fractures, leading to skeletal deformity (3). The function of LRP5 in eye development is complex; however, many studies suggest that it is essential for the normal regression of embryonic vasculature in the eye. Other minor features of OPPG include musculoskeletal problems like short stature, hypotonia, ligament laxity, intellectual impairment, and cardiac anomalies. We present a case of an infant, diagnosed as OPPG, who had unusual multiple fractures initially diagnosed with metabolic bone disease on screening, who had unusual multiple fractures despite treatment.
Case presentation
A very preterm neonate (28+5 weeks GA), extremely low birth weight of 730 g (Small for gestational age), born by preterm vaginal delivery with a significant antenatal history of preeclampsia in the mother and absent end diastolic flow on antenatal Doppler developed perinatal depression requiring bag and mask ventilation for one minute. The baby had respiratory distress syndrome and was on oxygen support for three days. Intravenous fluid was tapered and stopped by day 2, and Ryle's tube feeds were introduced gradually. Routine preterm screenings were done, which showed grade 2 intraventricular hemorrhage on the ultrasonography skull on day of life 3 (DOL-3), which was resolved on subsequent scans. Zone 2 stage 3 retinopathy of prematurity was noted on ophthalmic evaluation and metabolic bone disease workup was positive on DOL-28 with a vitamin D value of 4.3 ng/ml, calcium was 8.0 mg/dl, and phosphorus was 3 mg/dl, for which supplements were increased to therapeutic doses. The baby was gradually shifted to oral bondla feeds and had adequate weight gain. On DOL-80, painful, restricted motion of the left upper limb and right lower limb was noticed, for which an infantogram was done. The infantogram showed marked osteopenia and multiple fractures detected in the upper limb: right humerus mid-shaft, right proximal ulna, left distal end radius and right tibia fracture (Figures 1 and 2). Repeat vitamin D and calcium levels were done, which were in the normal range (Table 1). In view of multiple fractures and dysmorphism (proptosis, low-set ears, triangular facies, pointed chin), a clinical exome was sent suspecting skeletal dysplasia. The exome detected LRP5 mutation s/o OPPG. A detailed ophthalmic evaluation was done to screen for vision, and retinal pathologies, but the ophthalmic examination was normal. Supplements were continued and fractures were treated conservatively with casts. On follow-up, the baby was doing well and had good weight gain. Although fractures were healed, there was a mild left arm deformity post-healing (Figure 3). The plan is to start bisphosphonates, and conduct close IQ, developmental, and ophthalmic assessments for early detection and intervention.
Osteoporosis-pseudoglioma syndrome is a disorder caused by a mutation in the LRP5 (LDL receptor protein receptor 5) gene, located on chromosome 11q13.4 (1). Osteoporosis leads to bone deformities and fractures. With a typical history of minimal trauma, the time of onset and severity of the osteoporosis is highly variable (2). As the osteopaenic process stabilizes with age, prophylaxis and specialist care for fractures and deformities are essential to prevent incapacitating long-term problems. Intravenous bisphosphonate therapy may prevent fractures, leading to skeletal deformity (3). The function of LRP5 in eye development is complex; however, many studies suggest that it is essential for the normal regression of embryonic vasculature in the eye. Other minor features of OPPG include musculoskeletal problems like short stature, hypotonia, ligament laxity, intellectual impairment, and cardiac anomalies. We present a case of an infant, diagnosed as OPPG, who had unusual multiple fractures initially diagnosed with metabolic bone disease on screening, who had unusual multiple fractures despite treatment.
Case presentation
A very preterm neonate (28+5 weeks GA), extremely low birth weight of 730 g (Small for gestational age), born by preterm vaginal delivery with a significant antenatal history of preeclampsia in the mother and absent end diastolic flow on antenatal Doppler developed perinatal depression requiring bag and mask ventilation for one minute. The baby had respiratory distress syndrome and was on oxygen support for three days. Intravenous fluid was tapered and stopped by day 2, and Ryle's tube feeds were introduced gradually. Routine preterm screenings were done, which showed grade 2 intraventricular hemorrhage on the ultrasonography skull on day of life 3 (DOL-3), which was resolved on subsequent scans. Zone 2 stage 3 retinopathy of prematurity was noted on ophthalmic evaluation and metabolic bone disease workup was positive on DOL-28 with a vitamin D value of 4.3 ng/ml, calcium was 8.0 mg/dl, and phosphorus was 3 mg/dl, for which supplements were increased to therapeutic doses. The baby was gradually shifted to oral bondla feeds and had adequate weight gain. On DOL-80, painful, restricted motion of the left upper limb and right lower limb was noticed, for which an infantogram was done. The infantogram showed marked osteopenia and multiple fractures detected in the upper limb: right humerus mid-shaft, right proximal ulna, left distal end radius and right tibia fracture (Figures 1 and 2). Repeat vitamin D and calcium levels were done, which were in the normal range (Table 1). In view of multiple fractures and dysmorphism (proptosis, low-set ears, triangular facies, pointed chin), a clinical exome was sent suspecting skeletal dysplasia. The exome detected LRP5 mutation s/o OPPG. A detailed ophthalmic evaluation was done to screen for vision, and retinal pathologies, but the ophthalmic examination was normal. Supplements were continued and fractures were treated conservatively with casts. On follow-up, the baby was doing well and had good weight gain. Although fractures were healed, there was a mild left arm deformity post-healing (Figure 3). The plan is to start bisphosphonates, and conduct close IQ, developmental, and ophthalmic assessments for early detection and intervention.
.PNG)
.PNG)
.PNG)
.PNG)
Discussion
Osteoporosis-pseudoglioma syndrome due to mutations in LRP5 gene. LRP5 is a co-receptor of the Wnt signaling pathway and is situated in the osteoblast membrane between two other receptors, Frizzled 4 and Kremen. The Wnt pathway is involved in cell proliferation, adhesion, migration, and other activities. The binding of Frizzled 4 and LRP5 to Wnt stabilizes beta-catenin and activates bone formation (4,5). LRP5 regulates bone mineral density and is important for maintaining skeletal homeostasis; therefore, this disease presents with osteoporosis. Primary osteoporosis is seen in children with a heterozygous variant of LRP5 mutation (6). OPPG is characterized by osteoporosis and eye abnormalities that lead to vision loss. Ophthalmic findings vary from phthisis bulbi to less severe vitreoretinal findings, such as persistent hyperplasia of the primary vitreous (PHPV), congenital retinal folds, and exudative retinopathy. Fractures are more commonly seen after two years of life (7). Eye examination, coupled with bone phenotype and research of LRP5 mutation, are key points for diagnosing OPPG. It is an autosomal recessive condition each parent carries one copy of the mutated gene, and is asymptomatic for the condition; however, some carriers may have decreased bone mineral density. Bisphosphonates allow fracture prevention, improvement in bone mineral density, and enhanced mobility in children with OPPG (8). For children and adolescents diagnosed with OPPG who do not respond to other conventional therapies, short courses of teriparatide therapy may be helpful (9). New drugs favoring osteoblast function and osteoclast inhibition are potential candidates in the treatment of OPPG (10).
Conclusion
The clinician should differentiate OPPG from osteogenesis imperfecta and child abuse. This case portrays a rare presentation of OPPG syndrome, as the child presented with multiple fractures in infancy itself, the disease process was exaggerated due to the underlying metabolic bone disease, and the child did not have any ophthalmic findings which are generally diagnosed in infancy. The child is currently appropriate for corrected gestational age and follows objects. Close ophthalmic follow-up has been advised.
Acknowledgement
The authors thank the Dean, Topiwala National Medical College and BYL Nair Hospital for giving the opportunity to publish this manuscript.
Funding sources
Nil.
Ethical statement
The authors certify that they have obtained all appropriate patients’ parent consent.
Conflicts of interest
There are no conflicts of interest.
Author contributions
All the authors have read and approved the final version of the manuscript and agree to be accountable for the content presented.
Research Article: Case Report |
Subject:
Laboratory Sciences
Received: 2023/10/10 | Accepted: 2024/04/6 | Published: 2025/04/16 | ePublished: 2025/04/16
Received: 2023/10/10 | Accepted: 2024/04/6 | Published: 2025/04/16 | ePublished: 2025/04/16
References
1. Biha N, Ghaber SM, Hacen MM, Collet C. Osteoporosis-Pseudoglioma in a Mauritanian Child due to a Novel Mutation in LRP5. Case Rep Genet 2016; 2016: 9814928. [View at Publisher] [DOI] [PMID] [Google Scholar]
2. McDowell CL, Moore JD. Multiple fractures in a child: the osteoporosis pseudoglioma syndrome. A case report. J Bone Joint Surg Am. 1992; 74(8): 1247-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
3. Tüysüz B, Bursalı A, Alp Z, Suyugül N, Laine CM, Mäkitie O. Osteoporosis-pseudoglioma syndrome: three novel mutations in the LRP5 gene and response to bisphosphonate treatment. Horm Res Paediatr. 2012; 77(2): 115-20. [View at Publisher] [DOI] [PMID] [Google Scholar]
4. Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, et al. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13. Am J Hum Genet. 1996; 59(1): 146-51. [View at Publisher] [PMID] [Google Scholar]
5. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001; 107(4): 513-23. [View at Publisher] [DOI] [PMID] [Google Scholar]
6. Hartikka H, Mäkitie O, Männikkö M, Doria AS, Daneman A, Cole WG, et al. Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children. J Bone Miner Res. 2005; 20(5): 783-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
7. Ai M, Heeger S, Bartels CF, Schelling DK, Osteoporosis-Pseudoglioma Collaborative Group. Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet. 2005; 77(5): 741-53. [View at Publisher] [DOI] [PMID] [Google Scholar]
8. Streeten EA, McBride D, Puffenberger E, Hoffman ME, Pollin TI, Donnelly P, et al. Osteoporosis-pseudoglioma syndrome: Description of 9 new cases and beneficial response to bisphosphonates. 2008; 43(3): 584–90. [View at Publisher] [DOI] [PMID] [Google Scholar]
9. Homaei A, Chegini V, Saffari F. Clinical response to treatment with teriparatide in an adolescent with osteoporosis-pseudoglioma syndrome (OPPG): A case report. Int J Endocrinol Metab. 2022; 20(2): e121031. [View at Publisher] [DOI] [PMID] [Google Scholar]
10. Papadopoulos I, Bountouvi E, Attilakos A, Gole E, Dinopoulos A, Peppa M, et al. Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece. Eur J Pediatr. 2019; 178(3): 323-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Enamad
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.