The "4A" Syndrome: Adrenocortical Insufficiency Associated with Achalasia, Alacrima, Autonomic and Other Neurological Abnormalities

Overview

Journal Eur J Pediatr

Specialty Pediatrics

Date 1995 Jan 1

PMID 7895750

Citations 35

Authors

M Gazarian

C T Cowell

M BONNEY

W G GRIGOR

Affiliations

Soon will be listed here.

Abstract

The triad of adrenocortical insufficiency with alacrima and achalasia is an unusual disease entity in paediatrics. The association of autonomic and peripheral neuropathies has more commonly been reported in older individuals. We describe four children (two siblings) with this disorder, aged between 3 and 6 years at diagnosis, all of whom had clinical neurological abnormalities when examined between 6 and 8 years of age. In addition, we performed cardiovascular autonomic testing in three subjects: heart rate variation during deep breathing was abnormal in all three; Valsalva ratio was abnormal in two; and postural systolic blood pressure response was abnormal in one. Pupillary reflexes were abnormal in the only subject in which they could be measured. These results indicate that subtle neurological and, in particular, autonomic abnormalities can be detected at an early age. We propose that autonomic neuropathy be considered as an integral feature of this rare condition and suggest the term "4A" syndrome as a useful mnemonic for the association of adrenocortical insufficiency, achalasia and alacrima with autonomic and other neurological abnormalities.

Citing Articles

Very early and severe presentation of Triple A syndrome - case report and review of the literature.

Cehic M, Mitrovic K, Vukovic R, Milenkovic T, Kovacevic G, Todorovic S Front Endocrinol (Lausanne). 2024; 15:1431383.

PMID: 39387047 PMC: 11462544. DOI: 10.3389/fendo.2024.1431383.

Fertility and sexual activity in patients with Triple A syndrome.

Dumic K, Heinrichs C, Koehler K, Huebner A, Dumic M, Kusec V Front Endocrinol (Lausanne). 2024; 15:1357084.

PMID: 38544685 PMC: 10967945. DOI: 10.3389/fendo.2024.1357084.

Alacrimia in a case of suspected achalasia: A phenotypic variation of triple A syndrome?.

Dash N, Panda B Indian J Ophthalmol. 2023; 71(4):1659-1660.

PMID: 37026322 PMC: 10276738. DOI: 10.4103/IJO.IJO_2814_22.

The first report of a known 4A syndrome patient with suspected manifestations of COVID-19, what was the final outcome?.

Azmoodeh E, Kheirieh A, Mahdavi S, Toufan F, Nazemi S Heliyon. 2022; 8(12):e11766.

PMID: 36440457 PMC: 9675088. DOI: 10.1016/j.heliyon.2022.e11766.

Sporadic Triple A (Allgrove) Syndrome with Novel Tandem Mutations.

Miyazawa H, Kimura M, Yonezawa H, Maeda T Intern Med. 2020; 60(5):799-802.

PMID: 33087664 PMC: 7990642. DOI: 10.2169/internalmedicine.5201-20.

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