Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAASgene: a case report

Brooks, Brian P.; Kleta, Robert; Caruso, Rafael C.; Stuart, Caroline; Ludlow, Jonathan; Stratakis, Constantine A.

doi:10.1186/1471-2415-4-7

Cited by 47 publications

(44 citation statements)

References 25 publications

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“…Ophthalmic and neuro-ophthalmologic manifestations, such as abnormal pupillary reflex, anisocoria, optic atrophy and Horner's syndrome seem common [5,9,14,15,22]. Abnormal pupillary reactivity can be interpreted as a sign of dysautonomia [5].…”

Section: Discussionmentioning

confidence: 97%

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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Section: Discussionmentioning

confidence: 97%

Neurological features in adult Triple-A (Allgrove) syndrome

et al. 2011

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“…The loss of tear production probably results from the dysfunction of the of parasympathic part of autonomic nervous system and may lead to punctiform corneal destruction [3]. In all our patients, except one, decreased tear production was either present from birth or was noted in the first year of life.…”

Section: Discussionmentioning

confidence: 97%

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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“…46 The Allgrove locus is on chromosome 12q13. [45][46][47] Mutations have been found in the AAAS gene, which codes for the WD-repeat-containing ALADIN (alacrima-achalasia-adrenal insufficiency-neurologic disorder) protein. 48 It is interesting to note that there is significant clinical variability between patients with the same AAAS mutation, suggesting genetic heterogeneity.…”

Section: Allgrove Syndromementioning

confidence: 99%

“…40,41 The autonomic ocular findings include alacrima, keratoconjunctivitis sicca, lacrimal gland atrophy, pupillary abnormalities with hypersensitivity to dilute pilocarpine, and inappropriate accommodation. [43][44][45] Autonomic dysfunction also results in orthostatic hypotension with preservation of compensatory tachycardia and affects secretions so that sweating and oral secretions are diminished and males suffer sexual impotence. 46 The Allgrove locus is on chromosome 12q13.…”

Section: Allgrove Syndromementioning

confidence: 99%

Pediatric Autonomic Disorders

2006

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The scope of pediatric autonomic disorders is not well recognized. The goal of this review is to increase awareness of the expanding spectrum of pediatric autonomic disorders by providing an overview of the autonomic nervous system, including the roles of its various components and its pervasive influence, as well as its intimate relationship with sensory function. To illustrate further the breadth and complexities of autonomic dysfunction, some pediatric disorders are described, concentrating on those that present at birth or appear in early childhood.www.pediatrics.org/cgi

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Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAASgene: a case report

Cited by 47 publications

References 25 publications

Neurological features in adult Triple-A (Allgrove) syndrome

Neurological features in adult Triple-A (Allgrove) syndrome

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

Pediatric Autonomic Disorders

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