Neurological and adrenal dysfunction in the adrenal insufficiency/alacrima/achalasia (3A) syndrome.

Abstract

Review of 20 patients with glucocorticoid deficiency (three cases also with salt loss) associated with absent tear secretion (19 cases) and sensory neuropathy have also been described,89 together with ataxia, optic atrophy and impaired intelligence, "I indicating that the disorder has a wide spectrum of clinical manifestations. This paper describes the findings in a multicentre collaborative study carried out to ascertain the incidence of disordered neurological and automatic funciton in the syndrome. MethodsIn order to obtain information on patients with the adrenal insufficiency/alacrima/achalasia syndrome in the UK, questionnaires were sent to 39 senior members of the British Society for Paediatric Endocrinology asking for information on any cases under their care. Thirty seven questionnaires were returned, and six cases with the disorder were identified in the UK (cases 4, 5, 6, 13, 15, 17 described below).To increase the number of patients available for study, members of the European Society for Paediatric Endocrinology known to have had patients with the disorder under their care were invited to participate in the study and were sent questionnaires asking for information on the presence of adrenal insufficiency, alacrima, achalasia of the cardia, abnormal neurological findings, tests of autonomic function, evidence of intellectual impairment, skin manifestations, and family history.In some families siblings have died in early infancy, probably as a result of adrenal insufficiency. These have not been included in the study as little information is available on their neurological status.

The 4A Syndrome Association with Osteoporosis.

“…Since then a number of similar cases have been reported in the literature [2][3][4][5][6][7][8][9][10][11]. Triple A syndrome; characterised by adrenal insufficiency, achalasia and alacrima, is a rare disorder.…”

Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe

“…It is generally recognized that alacrima is the earliest and most consistent clinical feature of triple A syndrome. 8,11,12 Only after genetic confirmation of the diagnosis, when we specifically asked for additional typical symptoms, our patient reported mild swallowing difficulties, and an incipient achalasia was detected. Whether the p.Leu430Phe mutation is associated also with adrenal insufficiency can not be fully predicted at this point.…”

“…7 We conclude that the leucine 430 mutation does not interfere with the correct targeting of ALADIN to the NPC but may rather be critical for the interaction of ALADIN with other protein(s) of the nuclear Before the discovery of AAAS mutations as the molecular cause for the triple A syndrome, it had already been pointed out that the significant neurological problems are common in this multisystem disorder. 11 In a series of 20 families with clinical features of triple A syndrome, a wide spectrum of associated neurological abnormalities in all patients with triple A phenotype with and without proven AAAS mutations has been reported. 8 The progressive neurological syndrome observed in eight patients from six families comprised pupillary and other cranial nerve abnormalities, optic atrophy, autonomic neuropathy as well as upper and lower motor neuron signs.…”

A Case Report of Allgrove Syndrome with Neurological Involvement

“…Our patient was diagnosed with achalasia using barium graphy. Another sort of the disease involvement is the neurological complications which occurs during progressive stage of the disorder and at later ages [8]. Neurological involvement manifests itself as motor and sensory peripheral neuropathy, orthostatic hypotension, light reflex anomalies, xerophthalmia, extrapyramidal symptoms, and cardiac autonomic neuropathy [9].…”