Neurological features in adult Triple-A (Allgrove) syndrome

Abstract

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.

Novel Mutation in the AAAS Gene in a Severely Affected Triple-A Syndrome Patient

“…The neurological symptoms varies with some patients displaying a slowly worsening Amyotrophic Lateral Sclerosis (ALS)-like disorder, other patients suffer from multisystemic neurological disorders with cognitive involvement, cerebellar dysfunction, dysautonomia, ataxia and neuro-ophthalmologic symptoms. Neurological symptoms are often predominant in late onset Triple-A syndrome in adults [17]. Our patient had the clinical diagnosis at the onset of the autonomic symptoms; however he went to both a neurologist and a cardiologist before physicians could link his autonomic symptoms to the syndrome.…”

Edentulous child with Allgrove syndrome: a rare case report

“…While ACTH insensitivity could barely have manifestation such as asthenia, it might be wrongly diagnosed as muscle fatigue. The hormone values must be checked-up yearly because acute adrenal crisis could lead to sudden death4).…”

“…Sudden death can occur because of adrenal crisis. Some affected individuals show slowly progressive neurological symptom such as dysautonomia and bulbar involvement4). Allgrove syndrome is very rare and one such case was presented to us as an edentulous child.…”

Poorly Controlled Congenital Hypothyroidism due to an Underlying Allgrove Syndrome

“…In 2000, it was discovered that mutations in the AAAS gene on chromosome 12q13 (encoding the Aladin protein) underlie Allgrove syndrome [9] . Allgrove syndrome typically presents in childhood with dysphagia or hypoglycemia (due to adrenal crisis) as first symptom [10] , although it has also been described to present as late as in adulthood with neurological symptoms as presenting sign [11] . Alacrima is retrospectively often the first and most specific finding, but is easily neglected [12] .…”