Two Cases of Allgrove Syndrome with Mutations in the AAAS Gene

Endocrine Journal

Noriyuki KATSUMATA⁴  Saori KINJO²  Hitoshi KOHNO²  Megumi TAKEMOTO¹  Kenichi MIYAKO¹  Toshiaki TANAKA³ 

[1] Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University;Department of Endocrinology and Metabolism, Fukuoka Children's Hospital;Division of Endocrinology and Metabolism, National Center for Child Health and Development;Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development

关键词: Allgrove syndrome;    AAAS gene;    Adrenal insufficiency;    Achalasia;    Alacrima;   

DOI  :  10.1507/endocrj.51.473

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(14)Cited-By(5)Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. In the present study, we report two new patients of Allgrove syndrome with mutations in the AAAS gene. Patient 1 was a 22-year-old Japanese woman, born to consanguineous parents. She was confirmed to have adrenal insufficiency at the age of 3 years and 6 months. She developed alacrima and bilateral optic nerve atrophy at the age of 8 years. She had been noticed to have dysphagia. Based on these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis revealed a novel homozygous point mutation in exon 7 of her AAAS gene, changing codon 194 encoding Arg (CGA) to a stop codon (TGA) (R194X). Patient 2 was a 7-year-old Japanese boy, born to consanguineous parents. At the age of 1 year, he was noticed to be unable to produce tears. He was confirmed to have adrenal insufficiency, mental retardation and spastic diplegia at the age of 5 years and 4 months. He was tentatively diagnosed as having Allgrove syndrome, although he has never complained of dysphasia. Mutation analysis revealed a homozygous point mutation in exon 4 of his AAAS gene, changing codon 119 encoding Arg (CGA) to a stop codon (TGA) (R119X). Both of the R119X and R194X mutations are predicted to result in truncated and non-functioning ALADIN proteins, and thus the diagnosis of Allgrove syndrome was confirmed by the mutation analyses. These findings indicate that there exist significant clinical variability and mutational heterogeneities in Japanese patients with this syndrome.

【 授权许可】

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