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The clinical and laboratory features of patients with triple A syndrome: a single-center experience in Turkey

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Abstract

Aim

Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia, and alacrimia. This disorder is caused by mutations in the AAAS gene. The aim of this study is to discuss the clinical, laboratory and molecular genetic analysis results of 12 patients with TAS.

Method

We evaluated 12 patients from 8 families. Clinical and laboratory data were retrospectively collected from the medical records of the patients in the database for the period 2015–2020. All exons and exon-intron junctions of the AAAS gene were evaluated by next-generation sequencing method. Detected variants were classified according to American Collage of Medical Genetics criteria.

Results

Alacrimia was found in all patients (100%); achalasia was found in 10 patients (83.3%) and adrenal insufficiency was found in 10 patients (83.3%). In addition, hyperreflexia(6/12), learning disability(5/12), hypernasal speech(5/12), muscle weakness(8/12), delayed walking(7/12), delayed speech(6/12), excessive sweating(7/12), optic atrophy(1/12), epilepsy(1/12), palmoplantar hyperkeratosis(5/12), multiple dental caries(9/12), atrophy of the thenar/hypothenar muscles(4/12) and short stature(4/12) were detected. The DHEA-S levels were measured in 10 patients and were found to be low in 8 of them. In all patients, the sodium and potassium levels were found to be normal. AAAS gene sequencing revealed four previously reported c.1066_1067del (p.Leu356fs*8), c.1432 C > T (p.Arg478*), c.688 C > T (p.Arg230*), and c.1368_1372del (p.Gln456fs*38) variants and two novel homozygous c.1250-1 G > A and c.398_399 + 2del variants in the AAAS gene.

Conclusion

We detected two novel variants in the AAAS gene. While the classic triad is present in 66.7% of the cases, neurological dysfunction, skin and dental pathologies also occur quite frequently. The earliest and most common finding of TAS is alacrimia. Therefore, adrenal insufficiency should be investigated in all patients with alacrimia and if necessary, genetic analysis should be performed for TAS. In addition, TAS should be followed up with a multidisciplinary approach since it involves many systems.

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Authors and Affiliations

  1. Department of Pediatric Endocrinology, Diyarbakir Children’s Hospital, Diyarbakır, Turkey

    Ruken Yıldırım

  2. Faculty of Medicine, Department of Pediatric Endocrinology, Dicle University, Diyarbakır, Turkey

    Edip Unal

  3. Department of Medical Genetics, Gazi Yasargil Training and Research Hospital, Diyarbakir, Turkey

    Aysel Tekmenuray-Unal

  4. Department of Pediatric Endocrinology, Gazi Yaşargil Training and Research Hospital, Diyarbakır, Turkey

    Funda Feryal Taş & Şervan Özalkak

  5. Department of Pediatric Endocrinology, Health Sciences University, Erzurum Training and Research Hospital, Erzurum, Turkey

    Atilla Çayır

  6. Faculty of Medicine, Department of Pediatric Endocrinology, Artuklu University, Mardin, Turkey

    Mehmet Nuri Özbek

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Correspondence to Ruken Yıldırım.

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The study was performed in accordance with the rules of Declaration of Helsinki and approved by the Institutional Ethics Committee of Gazi Yaşargil Training and Research Hospital (Document number: 22.07.2022/142).

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Since the study was retrospective, informed consent was not available from the parents of the patients.

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Yıldırım, R., Unal, E., Tekmenuray-Unal, A. et al. The clinical and laboratory features of patients with triple A syndrome: a single-center experience in Turkey. Endocrine 79, 376–383 (2023). https://doi.org/10.1007/s12020-022-03206-5

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