MMP13-related metaphyseal dysplasia: a differential diagnosis of rickets

Abdulkerim Kolkiran; Tuğba Daşar; Abdullah Sezer

doi:10.1515/jpem-2025-0041

Article

MMP13-related metaphyseal dysplasia: a differential diagnosis of rickets

Abdulkerim Kolkiran , Tuğba Daşar and Abdullah Sezer

Published/Copyright: June 13, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 11

Abstract

Objectives

MMP13-related metaphyseal dysplasia Spahr type, is an extremely rare skeletal disorder, and only a dozen patients with a confirmed molecular diagnosis have been reported. It is characterized by mild short stature, genu varum, and metaphyseal irregularities including fraying, splaying, and cupping of the long bones. The disorder is in the differential diagnosis of rickets, a relatively common disorder in childhood that shares similar clinical and radiological features with metaphyseal dysplasia.

Case presentation

Herein, we present a 39-month-old girl patient who was initially evaluated for rickets due to mild short stature, bowing of the lower extremities, and metaphyseal changes. Biochemical tests including calcium, phosphate, alkaline phosphatase, and vitamin D levels were all within normal ranges. Radiographies revealed advanced bone age, mildly enlarged epiphyses, wide and irregular metaphyses of the long tubular bones, mildly thickened long tubular bones, and coxa vara. Clinical exome sequencing identified a homozygous variant in the MMP13 gene, confirming the diagnosis of metaphyseal dysplasia Spahr type.

Conclusions

We emphasize that metaphyseal dysplasias mimic the clinical and radiographic features of rickets and play a significant role in the differential diagnoses, particularly in patients presenting with short stature, genu varum, and metaphyseal irregularities, despite the absence of biochemical abnormalities. In accordance with the Nosology of Genetic Skeletal Disorders: 2023 Revision, we reinforce the dyadic naming system for the two groups of MMP13-related metaphyseal dysplasia, differentiated solely by their inheritance patterns, which also exhibit consistency with the location of the variants.

Keywords: clinical exome sequencing; MMP13-related autosomal recessive metaphyseal dysplasia; skeletal dysplasia; Spahr type

Corresponding author: Abdulkerim Kolkiran, Department of Paediatric Genetics, Etlik City Hospital, Halil Sezai Erkut Street, 06170, Ankara, Türkiye, E-mail: kolkiranaa@gmail.com

Acknowledgments

The authors express their gratitude to the patient and their family for their participation and cooperation in this study, as well as to Biologist Merve Ulak, on behalf of the genetic laboratory personnel, for their contribution to the molecular genetic testing.

Research ethics: Not applicable.
Informed consent: Informed consent was obtained from the family of the case included in this study.
Author contributions: Study conception and design: Abdulkerim Kolkiran, Tuğba Daşar. Data collection: Abdulkerim Kolkiran, Tuğba Daşar, Abdullah Sezer. Analysis and interpretation of results: Abdullah Sezer. Draft manuscript preparation: Abdulkerim Kolkiran, Tuğba Daşar, Abdullah Sezer.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2025-01-19

Accepted: 2025-05-27

Published Online: 2025-06-13

Published in Print: 2025-11-25

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https://doi.org/10.1515/jpem-2025-0041

Keywords for this article

clinical exome sequencing; MMP13-related autosomal recessive metaphyseal dysplasia; skeletal dysplasia; Spahr type