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Low DHEAS Concentration in a Girl Presenting with Short Stature and Premature Pubarche: A Novel PAPSS2 Gene Mutation.
Horm Res Paediatr 2019; :1-7HR

Abstract

OBJECTIVE

Dehydroepiandrosterone (DHEA) sulfotransferase (SULT2A1) converts DHEA to DHEA sulfate (DHEAS) which prevents bioactive androgen excess. This enzymatic reaction requires PAPS (3'-phospho-adenosine-5'-phosphosulfate) biosynthesis mediated by PAPS synthase 2 (PAPSS2). Here, we report a patient presenting with short stature and premature pubarche due to a novel homozygous mutation in the PAPPS2 gene.

CASE REPORT

A 7.5-year-old girl was referred for short stature. She was born at term with a birth weight of 2,850 g and her parents were first cousins. At presentation, her height was 113.0 cm (-2.1 SDS) and weight was 28.3 kg (+0.9 SDS), her arm span was 115.0 cm, and upper to lower segment ratio was 1.2. Her pubic hair and breast development were at Tanner stage III and I, respectively. Radiographs revealed mild lumbar scoliosis and platyspondyly and irregular vertebral endplates in the thoracolumbar region. Her serum DHEAS was low (39 ng/mL). The plasma DHEAS/DHEA ratio was significantly decreased on 2 separate measurements (4.4 and 19.8; normal range 31-345). PAPSS2 gene analysis identified a homozygous p.L440Wfs*12 (c.1318_1330 delCTACTACACCCTC) variant. This is the first report of a large deletion leading to a frameshift effect in the PAPSS2 gene and a truncated PAPSS2 protein.

CONCLUSION

We describe the third case with PAPSS2 deficiency presenting with premature pubarche, and the first large deletion in the PAPSS2 gene. Although PAPSS2 deficiency is a rare cause of premature pubarche and adrenal androgen excess, it should be considered, especially in cases with disproportionate short stature and clinical hyperandrogenism associated with low plasma DHEAS concentration.

Authors+Show Affiliations

Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey.Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey, zehra_yavas@yahoo.com.Department of Medical Genetics, Marmara University School of Medicine, Istanbul, Turkey.Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey.Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey.Department of Medical Genetics, Marmara University School of Medicine, Istanbul, Turkey.Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey.Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey.Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey.

Pub Type(s)

Case Reports

Language

eng

PubMed ID

31461705

Citation

Eltan, Mehmet, et al. "Low DHEAS Concentration in a Girl Presenting With Short Stature and Premature Pubarche: a Novel PAPSS2 Gene Mutation." Hormone Research in Paediatrics, 2019, pp. 1-7.
Eltan M, Yavas Abali Z, Arslan Ates E, et al. Low DHEAS Concentration in a Girl Presenting with Short Stature and Premature Pubarche: A Novel PAPSS2 Gene Mutation. Horm Res Paediatr. 2019.
Eltan, M., Yavas Abali, Z., Arslan Ates, E., Kirkgoz, T., Kaygusuz, S. B., Türkyılmaz, A., ... Guran, T. (2019). Low DHEAS Concentration in a Girl Presenting with Short Stature and Premature Pubarche: A Novel PAPSS2 Gene Mutation. Hormone Research in Paediatrics, pp. 1-7. doi:10.1159/000502114.
Eltan M, et al. Low DHEAS Concentration in a Girl Presenting With Short Stature and Premature Pubarche: a Novel PAPSS2 Gene Mutation. Horm Res Paediatr. 2019 Aug 28;1-7. PubMed PMID: 31461705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low DHEAS Concentration in a Girl Presenting with Short Stature and Premature Pubarche: A Novel PAPSS2 Gene Mutation. AU - Eltan,Mehmet, AU - Yavas Abali,Zehra, AU - Arslan Ates,Esra, AU - Kirkgoz,Tarik, AU - Kaygusuz,Sare Betul, AU - Türkyılmaz,Ayberk, AU - Bereket,Abdullah, AU - Turan,Serap, AU - Guran,Tulay, Y1 - 2019/08/28/ PY - 2019/05/13/received PY - 2019/07/13/accepted PY - 2019/8/29/entrez PY - 2019/8/29/pubmed PY - 2019/8/29/medline KW - Autosomal recessive brachyolmia KW - PAPSS2 KW - Premature pubarche KW - SULT2A1 KW - Spondyloepimetaphyseal dysplasia SP - 1 EP - 7 JF - Hormone research in paediatrics JO - Horm Res Paediatr N2 - OBJECTIVE: Dehydroepiandrosterone (DHEA) sulfotransferase (SULT2A1) converts DHEA to DHEA sulfate (DHEAS) which prevents bioactive androgen excess. This enzymatic reaction requires PAPS (3'-phospho-adenosine-5'-phosphosulfate) biosynthesis mediated by PAPS synthase 2 (PAPSS2). Here, we report a patient presenting with short stature and premature pubarche due to a novel homozygous mutation in the PAPPS2 gene. CASE REPORT: A 7.5-year-old girl was referred for short stature. She was born at term with a birth weight of 2,850 g and her parents were first cousins. At presentation, her height was 113.0 cm (-2.1 SDS) and weight was 28.3 kg (+0.9 SDS), her arm span was 115.0 cm, and upper to lower segment ratio was 1.2. Her pubic hair and breast development were at Tanner stage III and I, respectively. Radiographs revealed mild lumbar scoliosis and platyspondyly and irregular vertebral endplates in the thoracolumbar region. Her serum DHEAS was low (39 ng/mL). The plasma DHEAS/DHEA ratio was significantly decreased on 2 separate measurements (4.4 and 19.8; normal range 31-345). PAPSS2 gene analysis identified a homozygous p.L440Wfs*12 (c.1318_1330 delCTACTACACCCTC) variant. This is the first report of a large deletion leading to a frameshift effect in the PAPSS2 gene and a truncated PAPSS2 protein. CONCLUSION: We describe the third case with PAPSS2 deficiency presenting with premature pubarche, and the first large deletion in the PAPSS2 gene. Although PAPSS2 deficiency is a rare cause of premature pubarche and adrenal androgen excess, it should be considered, especially in cases with disproportionate short stature and clinical hyperandrogenism associated with low plasma DHEAS concentration. SN - 1663-2826 UR - https://www.unboundmedicine.com/medline/citation/31461705/Low_DHEAS_Concentration_in_a_Girl_Presenting_with_Short_Stature_and_Premature_Pubarche:_A_Novel_PAPSS2_Gene_Mutation L2 - https://www.karger.com?DOI=10.1159/000502114 DB - PRIME DP - Unbound Medicine ER -