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Mild progressive osseous heteroplasia overlap syndrome with PTH and TSH resistance appearing during adolescence and not early childhood

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Abstract

Purpose

Progressive osseous heteroplasia (POH), a genetic disorder, is associated with Albright’s hereditary osteodystrophy (AHO), pseudohypoparathyroidism, and primary osteoma cutis and has common features of superficial ossification and GNAS-inactivating mutations. Disorders due to GNAS-inactivating mutations are classified as “inactivating parathyroid hormone (PTH)/PTHrP signaling disorder type 2.” This study reports a case of mild POH overlap syndrome to improve understanding of genotype–phenotype correlations.

Methods

A 13-year and 6-month-old Japanese boy was referred to our hospital with a chief complaint of the lower limb length difference. He underwent clinical, biochemical, radiological, and genetic studies.

Results

He showed sporadic GNAS mutation, deep ectopic ossification, small for gestational age (SGA), congenital tooth defect, and lack of AHO features; he met the diagnostic criteria for POH, and mild PTH and TSH resistance was detected. He had constant hyperphosphatasemia and hypocalciuria. At the age of 10 years, he occasionally experienced high iPTH levels. The pituitary stimulation test showed a normal response of all hormones at 3 years of age, but TSH response was decreased (previously 0.770, peak value 4.144 μIU/mL) in the TRH loading test at age 13 years and 6 months. DNA analysis showed a heterozygous p.D189MfsTer14 mutation of GNAS. The parents did not carry this mutation.

Conclusion

We report a rare case of POH overlap syndrome with PTH/TSH resistance that appeared in adolescence rather than early childhood. Cases diagnosed with POH in early childhood also require reassessment during adolescence. Further studies of the GNAS heterozygous mutation p.D189MfsTer14 may reveal factors involved in POH overlap syndrome.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Kayo Ozaki, Akari Mituboshi & Masashi Nagai

  2. Department of Pediatrics, Kakogawa Chuo City Hospital, Kakogawa, Japan

    Atushi Nishiyama

  3. Center for Intractable Diseases, Saitama University Hospital, Saitama, Japan

    Gen Nishimura

  4. Department of Clinical Genetics, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Naoya Morisada

  5. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

    Kazumoto Iijima

Authors
  1. Kayo Ozaki
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  2. Akari Mituboshi
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  3. Masashi Nagai
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  4. Atushi Nishiyama
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  5. Gen Nishimura
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  6. Naoya Morisada
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  7. Kazumoto Iijima
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Contributions

Conceptualization and writing—original draft preparation: K.O.; formal analysis: N.M. and K.I.; investigation: G.N., A.M., and M.N.; resources: A.N.

Corresponding author

Correspondence to Kayo Ozaki.

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The authors declare no competing interests.

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Written informed consent was obtained from the patient and his parents for publication of this case report and any accompanying images.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Hyogo Prefectural Kobe Children’s Hospital committee + reference number: R3-1) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Ozaki, K., Mituboshi, A., Nagai, M. et al. Mild progressive osseous heteroplasia overlap syndrome with PTH and TSH resistance appearing during adolescence and not early childhood. Endocrine 74, 685–689 (2021). https://doi.org/10.1007/s12020-021-02821-y

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  • DOI: https://doi.org/10.1007/s12020-021-02821-y

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