Spondyloenchondrodysplasia with immune dysregulation: an under-the-radar cause of spasticity

Berkay Yalçınkaya; Ahmet Furkan Çolak; Hilmi Berkan Abacıoğlu; Alp Çetin

doi:10.12701/jyms.2025.42.30

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Image vignette Physical therapy, Sports Therapy, and Rehabilitation Spondyloenchondrodysplasia with immune dysregulation: an under-the-radar cause of spasticity: Berkay Yalçınkaya, Ahmet Furkan Çolak, Hilmi Berkan Abacıoğlu, Alp Çetin; Journal of Yeungnam Medical Science 2025;42:30.
DOI: https://doi.org/10.12701/jyms.2025.42.30
Published online: March 27, 2025

Department of Physical and Rehabilitation Medicine, Hacettepe University Medical School, Ankara, Türkiye

Corresponding Author: Berkay Yalçınkaya, MD Department of Physical and Rehabilitation Medicine, Hacettepe University Medical School, Zemin Kat, FTR AD, Sıhhiye, Ankara 06230, Türkiye Tel: +90-312-309-4142 Fax: +90-312-310-5769 E-mail: berkay0lka@gmail.com

• Received: March 8, 2025 • Revised: March 23, 2025 • Accepted: March 26, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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A 9-year-old male patient, referred from the neurology department, presented to our outpatient clinic with longstanding gait disturbance. According to the detailed history provided by his parents, the gait disturbance had gradually worsened over the past 6 years. Additionally, they reported restricted movements of the patient’s hips and ankles. No history of trauma, pain, paresthesia, weakness, swelling, or other complaints was noted. The patient’s prenatal and perinatal histories were unremarkable. However, motor growth retardation was observed during the postnatal period. The patient also developed atopic dermatitis and recurrent oral aphthous ulcers. Physical examination revealed restricted dorsiflexion of both ankles and limited internal and external rotations of both hips. Muscle strength and sensory examinations could not be accurately performed because of limited patient cooperation. The deep tendon reflexes in the lower extremities were hyperactive bilaterally, and spasticity was observed in several muscle groups, including the hip adductors, knee extensors, and ankle plantar flexors. Gait analysis revealed toe walking (Supplementary Video 1). The other physical examination findings were within normal limits. Laboratory tests showed lymphopenia (2.7×10³/µL; range, 6–9×10³/µL) and reduced immunoglobulin M levels (60.8 mg/dL; range, 78–261 mg/dL). Radiographs of the posteroanterior and lateral spine, along with the bilateral hips, knees, and feet, demonstrated platyspondyly (flattened vertebral bodies) and metaphyseal irregularities (Fig. 1). Cranial magnetic resonance imaging revealed cerebral atrophy and corpus callosum thinning (Fig. 2). Given these symptoms and findings, genetic analysis had previously confirmed a diagnosis of spondyloenchondrodysplasia with immune dysregulation (SPENCDI), identifying a mutation in the acid phosphatase 5, tartrate resistant (ACP5) gene (Table 1).

To treat spasticity, botulinum toxin injections were administered using the seeding technique into the innervation zones of the gastrocnemius, soleus, medial hamstring, and tibialis posterior muscles. The seeding technique provides more target-specific and effective botulinum toxin injections, leading to more favorable functional outcomes [1]. Oral baclofen was administered at a dose of 5 mg twice daily. An ankle-foot orthosis was prescribed along with a home exercise program focusing on range of motion and stretching. The patient was scheduled for regular follow-ups, and a slight improvement in his condition was observed. The patient is still undergoing regular follow-ups.

SPENCDI is an exceptionally rare autosomal recessive disorder caused by mutations in ACP5, which encodes the tartrate-resistant acid phosphatase (TRAP) enzyme [2]. These mutations reduce TRAP activity and subsequently increase osteopontin phosphorylation, promoting osteoclastic activity and ultimately resulting in skeletal pathologies that include bone and cartilage defects [3]. Clinically, SPENCDI is characterized by skeletal dysplasia, immunological dysfunction, and neurological impairment. Musculoskeletal involvement commonly includes vertebral and metaphyseal dysplasia, enchondromas affecting the spine and long bones, platyspondyly, rhizomelia, and spinal deformities that manifest as short stature, gait abnormalities, and skeletal deformities. Immunological dysfunction can present as recurrent infections, immunodeficiency, thrombocytopenia, hemolytic anemia, systemic lupus erythematosus, or rheumatoid arthritis. Neurological manifestations may include ataxia, spasticity, intracranial calcification, and cognitive impairment [2] (Fig. 3).

The diagnosis of SPENCDI relies primarily on genetic testing, although family history and characteristic clinical features may also suggest the condition [3]. In pediatric patients presenting with a triad of musculoskeletal, immunological, and neurological symptoms, SPENCDI should be considered in the differential diagnosis, with genetic testing recommended in suspected cases. Although there is currently no definitive treatment for SPENCDI, immunological therapies are currently being investigated. Herein, we have presented a case of SPENCDI to raise awareness of this rare syndrome and emphasize its inclusion in the differential diagnosis of pediatric patients with musculoskeletal, immunological, and neurocognitive abnormalities. Early diagnosis and management are critical as they may positively influence the prognosis of patients with SPENCDI.

Supplementary materials

Supplementary Video 1 can be found at https://doi.org/10.12701/jyms.2025.42.30.

Supplementary Video 1.

A recording of the patient exhibiting toe walking at home.

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Ethics statement

Informed consent was obtained from the patients’s legal guardian.

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: all authors; Formal analysis, Supervision: AÇ; Investigation: BY, AFÇ, HBA; Writing-original draft: BY, AFÇ, HBA; Writing-review & editing: AÇ.

Fig. 1.

Radiographic images. (A) Posteroanterior and (B) lateral spine radiographs indicating platyspondyly (flattened vertebral bodies) (arrowheads). (C) Bilateral hip, (D) knee, and (E) foot radiographs demonstrating metaphyseal irregularities (arrowheads).

Fig. 2.

Cranial magnetic resonance imaging, T1-weighted sagittal view, depicting thinning of the corpus callosum (asterisks) and prominent cerebral sulci, consistent with cerebral atrophy.

Fig. 3.

Most common clinical findings of patients with spondyloenchondrodysplasia with immune dysregulation.

Table 1.

Whole exome sequencing analysis results

Gene	Transcript	Protein change	Nucleotide change	Zygosity	Classification
ACP5	NM_001111035.1	p.(Arg272Cys)	c.814C>T	Homozygous	Not classified

References

1. Kaymak B, Kara M, Abdulsalam AJ, Ricci V, Özçakar L. Optimizing botulinum toxin injections by minding the muscle architecture and its innervation zone: the '”seeding” technique. Can J Neurol Sci 2024 Nov 25 2024 [Epub]. https://doi.org/10.1017/cjn.2024.336.Article
2. Al-Kateb F, Dyab D, Almadani B, Al-Enezi N. Spondyloenchondrodysplasia with immune dysregulation, but without skeletal dysplasia, in a six-year-old boy: a case report. Cureus 2024;16:e60314. Article PubMed PMC
3. Gernez Y, Narula M, Cepika AM, Valdes Camacho J, Hoyte EG, Mouradian K, et al. Case report: refractory Evans syndrome in two patients with spondyloenchondrodysplasia with immune dysregulation treated successfully with JAK1/JAK2 inhibition. Front Immunol 2024;14:1328005.Article PubMed PMC

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Spondyloenchondrodysplasia with immune dysregulation: an under-the-radar cause of spasticity

Fig. 1. Radiographic images. (A) Posteroanterior and (B) lateral spine radiographs indicating platyspondyly (flattened vertebral bodies) (arrowheads). (C) Bilateral hip, (D) knee, and (E) foot radiographs demonstrating metaphyseal irregularities (arrowheads).

Fig. 2. Cranial magnetic resonance imaging, T1-weighted sagittal view, depicting thinning of the corpus callosum (asterisks) and prominent cerebral sulci, consistent with cerebral atrophy.

Fig. 3. Most common clinical findings of patients with spondyloenchondrodysplasia with immune dysregulation.

Fig. 1.

Fig. 2.

Fig. 3.

Spondyloenchondrodysplasia with immune dysregulation: an under-the-radar cause of spasticity

Gene	Transcript	Protein change	Nucleotide change	Zygosity	Classification
ACP5	NM_001111035.1	p.(Arg272Cys)	c.814C>T	Homozygous	Not classified

Table 1. Whole exome sequencing analysis results