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Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy

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Abstract

The clinical and molecular data on triple A syndrome in two siblings (girl 3.5 years and boy 5.5 years at presentation) with early onset of neurological dysfunction are described. Both patients showed delayed developmental milestones and neurological dysfunctions (motor and sensory demyelinating neuropathy, marked hyperreflexia, calves hypothrophy, pes cavus, gait disturbance) in early childhood, when erroneously diagnosed with hereditary polyneuropathy, most likely Charcot–Marie–Tooth disease. After a severe adrenal crisis in the younger sister at the age of 3 years, the older brother aged 5.5 years was also evaluated and latent adrenal insufficiency was discovered. As both of the siblings had alacrima, hyperkeratosis of palms, cutis anserina, and nasal speech, diagnosis of triple A syndrome was considered. Sequencing of the AAAS gene detected a compound heterozygous mutation consisting of a novel mutation p.Ser296Tyr (c.887C>A) in exon 9 and a previously described p.Ser263Pro (c.787T>C) missense mutation in exon 8 in both siblings. In conclusion, triple A syndrome should be considered in patients presenting with early neurological dysfunction and developmental delay. Alacrima as the earliest and most consistent clinical sign should be investigated by Schirmer test. Patients should be regularly tested for adrenal dysfunction to prevent life-threatening adrenal crises.

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Conflict of interest statement

The authors of this manuscript have no relevant financial relationship to declare.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Pediatrics, University Hospital Zagreb, Kišpatićeva 12, 10 000, Zagreb, Croatia

    Miroslav Dumić & Nataša Rojnić-Putarek

  2. Division of Neurology, Department of Pediatrics, University Hospital Zagreb, Zagreb, Croatia

    Nina Barišić

  3. Department of Laboratory Diagnostics, University Hospital Zagreb, Zagreb, Croatia

    Vesna Kušec

  4. School of Health Studies, University of Zagreb, Zagreb, Croatia

    Andrija Stanimirović

  5. Children’s Hospital, Technical University Dresden, Dresden, Germany

    Katrin Koehler & Angela Huebner

Authors
  1. Miroslav Dumić
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  2. Nina Barišić
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  3. Nataša Rojnić-Putarek
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  4. Vesna Kušec
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  5. Andrija Stanimirović
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  6. Katrin Koehler
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  7. Angela Huebner
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Correspondence to Miroslav Dumić.

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Dumić, M., Barišić, N., Rojnić-Putarek, N. et al. Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy. Eur J Pediatr 170, 393–396 (2011). https://doi.org/10.1007/s00431-010-1314-4

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  • DOI: https://doi.org/10.1007/s00431-010-1314-4

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