The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene

Salehi, Marzieh; Houlden, Henry; Sheikh, Arsalan; Poretsky, Leonid

doi:10.1016/j.metabol.2004.08.013

Cited by 16 publications

(10 citation statements)

References 25 publications

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“…We used high dose ACTH test (36 μg/kg b.w., max 250 μg), which failed to produce significant rise in cortisol level in six of our patients. However, Salehi et al have shown that in one adult genetically proven triple A syndrome patient, high dose ACTH test produced normal cortisol level, but adrenal insufficiency was diagnosed by low dose (1 μg) ACTH test and insulin-induced hypoglycemia [21]. This could probably explain unrecognized adrenal insufficiency and sudden death in severe hypoglycemia of patient no.…”

Section: Discussionmentioning

confidence: 98%

Triple A syndrome: 32 years experience of a single centre (1977–2008)

et al. 2010

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Triple A syndrome is an autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and neurodegeneration. Mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN have been reported in these patients. Over the period 1977-2008 we evaluated ten subjects with the clinical diagnosis of triple A syndrome. Molecular analysis was performed in seven patients and revealed that all except one are compound heterozygotes for two mutations in the AAAS gene. Two novel mutations were detected: c.123+2T>C resulted in splice defect while c.1261_1262insG mutation resulted in a truncated protein (p.V421fs), which most probably is not functional. Genotype-phenotype correlation could not be established. In all our patients, except one sibling of previously diagnosed brother and sister, genetic analysis was performed when at least two symptoms were present, usually alacrima and achalasia. Based on our experience, we recommend that in case of the presence of alacrima and at least one more symptom of triple A syndrome, adrenal function testing and molecular analysis should be performed. In all children with mutation in AAAS gene, regular follow up of adrenal function is necessary to avoid adrenal crisis and start substitution therapy as soon as adrenal insufficiency is noted.

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Section: Discussionmentioning

confidence: 98%

Triple A syndrome: 32 years experience of a single centre (1977–2008)

et al. 2010

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“…This discrepancy appears to be characteristic of this condition. However, other reports relate sensorimotor demyelination [25], motor myelin alterations [7], mixed axonal-demyelinating sensorimotor polyneuropathy [10] or anterior horn syndrome [14,18]. Questions about a possible additional myopathic process have been raised [23].…”

Section: Discussionmentioning

confidence: 99%

Neurological features in adult Triple-A (Allgrove) syndrome

et al. 2011

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Triple-A or Allgrove syndrome is a rare multisystem disease classically associated with esophageal achalasia, adrenal insufficiency and alacrima. Here, we describe the poorly understood neurological characteristics often associated with this condition, through the clinical and electrophysiological analysis of eight patients. All patients were genetically confirmed and had a mutation in the ALADIN gene. They all displayed a classical picture of Triple-A syndrome: all suffered from achalasia and alacrima and half of them from adrenal insufficiency. However, all harbored a neurological picture characterized by a recognizable pattern of peripheral neuropathy. Other neurological features included cognitive deficits, pyramidal syndrome, cerebellar dysfunction, dysautonomia, neuro-ophthalmological signs and bulbar and facial symptoms. This neurological picture was prominent in all patients and misled the initial diagnosis in six of them, which had a late onset. We then review the previous neurological reports of this disease, to improve the understanding of this rare condition. Diagnosis of late-onset Triple-A syndrome is difficult when the clinical picture is mainly neurological and when endocrine or gastrointestinal signs are minor. The characteristics of the peripheral neuropathy, among other neurological signs, can be of help.

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“…Such a delay in the diagnosis of adrenal insufficiency emphasizes the need for a correct assessment of the adrenal function in any young subject with achalasia or alacrima. In clinical practice, triple A-related adrenal insufficiency cannot be diagnosed only on the basis of the endocrine basal serum evaluation (ACTH and cortisol); it also requires dynamic tests [14], as in the investigation of the hypothalamic-pituitary adrenal axis in other clinical conditions [15]. …”

Section: Discussionmentioning

confidence: 99%

Late-Onset Triple A Syndrome: A Risk of Overlooked or Delayed Diagnosis and Management

et al. 2008

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Background/Aims: A 33-year-old man was referred for the first time to the Division of Neurology because of the presence and progression of neurological symptoms. Dysphagia, weakness, reduced tear production, and nasal speech were present. In order to point the attention of late-onset triple A syndrome we describe this case and review the literature. Methods: Hormonal and biochemical evaluation, Schirmer test, tilt test and genetic testing for AAAS gene mutations. Results: Late-onset triple A syndrome caused by a novel homozygous missense mutation in the AAAS gene (A167V in exon 6) was diagnosed at least 17 years after symptom onset. Conclusions: The association between typical signs and symptoms of triple A syndrome should suggest the diagnosis even if they manifest in adulthood. The diagnosis should be confirmed by Schirmer test, endocrine testing (both basal and dynamic), genetic analysis, and detailed gastroenterological and neurological evaluations. Awareness of the possible late onset of the disease and of diagnosis in adulthood is still poor among clinicians, the acquaintance with the disease is more common among pediatricians. The importance of an adequate multidisciplinary clinical approach, dynamic testing for early diagnosis of adrenal insufficiency and periodical reassessment of adrenal function are emphasized.

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The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene

Cited by 16 publications

References 25 publications

Triple A syndrome: 32 years experience of a single centre (1977–2008)

Triple A syndrome: 32 years experience of a single centre (1977–2008)

Neurological features in adult Triple-A (Allgrove) syndrome

Late-Onset Triple A Syndrome: A Risk of Overlooked or Delayed Diagnosis and Management

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