Bilateral Recurrent Laryngeal Nerve Palsy following Total Thyroidectomy in Triple A Syndrome, an Unexpected but Critical Complication

Introduction. Triple “A” syndrome (TAS) is a rare autosomal recessive disorder that presents in childhood with achalasia cardia, alacrima, ACTH-resistant adrenal insufficiency, with sensorimotor and autonomic polyneuropathy developing later in the course of the disease. Case Presentation. An adult white male affected by this syndrome underwent an uneventful total thyroidectomy for malignancy and suffered delayed bilateral recurrent laryngeal nerve palsy in the early postoperative hours. The palsy spontaneously resolved after a five-week course. Conclusion. Given the rarity of this severe condition and the absence of surgical or medical causes identifiable, there is possibility that it is the neurological involvement caused by TAS that predisposed the patient to this adverse outcome, precipitated by standard manipulations during surgery.

The Retina in Patients With Triple A Syndrome: A Window Into Neurodegeneration?

ObjectiveExperimental evidence suggests that the clinical manifestations of Triple A syndrome result from oxidative stress. Several conditions caused by oxidative stress display retinal involvement. Our objective was to assess the retina and optic nerve involvement in children with Triple A syndrome.MethodsEleven patients with genetically proven Triple A syndrome followed-up in our centre were approached for study participation. The main outcome was the measurement of the thicknesses of the different retinal layers by Optical Coherence Tomography (OCT).Results9 patients with triple A syndrome had OCT measurements. 7 patients were children and 2 were adults; 4 were females and 5 were males. The 7 paediatric patients had at least two OCT measured at a mean interval of 7.9 months after the first one. The average Retinal Nerve Fibre Layer thickness was 74 ± 10 µm in patients compared to the paediatric reference range of 100 ± 2 µm (p<0.05).Conclusions and RelevanceThis is the first study to document retinal layer thicknesses in a series of patients with Triple A syndrome. Nearly all retinal thickness and peripapillary RNFL measurements were very significantly inferior to the reference range in Triple A patients, whatever their age. RNFL thinning was more marked at the temporal part of the optic nerve. OCT being non-invasive, it represents a promising tool to assess the severity of neurodegeneration in patients with Triple A syndrome.

Neurophysiological Characteristics of Allgrove (Triple A) Syndrome: Case Report and Literature Review

Allgrove or “Triple A” syndrome is characterized by alacrima, achalasia, and adrenocorticotropic hormone-resistant adrenal insufficiency, as well as central and peripheral nervous system involvement. Patients demonstrate heterogeneity with regard to their age of symptom onset, disease severity, and nature of clinical symptoms. Neurophysiological testing has also shown variability ranging from: motor neuron disease with prominent bulbar involvement, motor-predominant neuropathy, or sensorimotor polyneuropathy with axonal or mixed axonal and demyelinating features. We report an 11-year-old boy who presented with neurological symptoms of progressive spasticity and peripheral neuropathy. His neurophysiological testing confirmed a sensorimotor polyneuropathy with axonal and demyelinating features. Exome sequencing identified compound heterozygote variants in the AAAS gene. We summarize the neurophysiological findings in him and 29 other patients with Allgrove syndrome where nerve conduction study findings were available thereby providing a review of the heterogeneity in neurophysiological findings that have been reported in this rare disorder.

Spectral Domain – Optical Coherence Tomography findings in Triple-A Syndrome – A case series from Pakistan

Triple A Syndrome is an autosomal recessive entity involving multiple systems usually characterized by adrenal insufficiency, alacrimia and achalasia. The disease features include variable degrees of neurological and neuro-ophthalmic manifestations. Protein ALADIN encoded by the AAAS gene is found to be defective in Triple A Syndrome. Here we discuss a case series of five patients diagnosed as Triple A Syndrome. Clinically there was variable degree of optic atrophy in all the cases, which was further confirmed with spectral domain Optical Coherence Tomography The aim of this study was to publish the OCT based ONFL graphs of these unique cases, so that being an ophthalmologist we can take a multidisciplinary approach and decisions accordingly. doi: https://doi.org/10.12669/pjms.37.1.3310 How to cite this:Nasir J, Javed A, Arshad O, Chatni MH. Spectral Domain – Optical Coherence Tomography Findings in Triple-A Syndrome – A case series from Pakistan. Pak J Med Sci. 2021;37(1):267-271. doi: https://doi.org/10.12669/pjms.37.1.3310 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Triple-A Syndrome (TAS): An In-Depth Overview on Genetic and Phenotype Heterogeneity

Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by three cardinal symptoms: alacrimia, achalasia and adrenal insufficiency due to ACTH insensitivity. Various progressive neurological abnormalities and skin changes have been described in association with the syndrome. The disease is caused by mutation in the AAAS gene on chromosome 12q13. Mutations in AAAS were identified in more than 90% of individuals and families with TAS. The protein encoded by AAAS was termed ALADIN and is part of the WD repeat family of proteins, that have been found to be involved in many different functions such as protein-protein interaction, RNA processing, cytoskeleton assembly, control of cell division, signal transduction and apoptosis. Immunohistochemical analysis showed that mutated or truncated ALADIN localizes to the cytoplasm rather than to the nuclear pore complex. The exact function of ALADIN and the mechanisms that lead to the ACTH-resistant adrenal phenotype remains largely unknown. Nonetheless, recent studies provided some insights on the role of ALADIN as a member of the Nuclear Pore Complex not only implicated in the import of proteins involved in DNA repair and oxidative stress homeostasis but also in the strengthening of the mitotic spindle assembly. Early identification of the syndrome is challenging, given the rarity of the condition and high phenotypic heterogeneity even among members of the same family. In this review, we aim to summarize the current knowledge of clinical and molecular profile of patients with TAS and recommendations for the diagnosis, management, and follow-up of patients.

Triple A syndrome: a case report

Triple A syndrome is a rare autosomal recessive disorder characterised by alacrimia, achalasia and adrenal failure. It was first reported by Allgrove in 1978 and 100 cases have been reported worldwide. This case report concerns a 24-year-old woman who was referred for evaluation of dysphagia and was finally diagnosed as such a case. A high degree of suspicion enables all the components of this syndrome to be searched for, as early diagnosis can reduce the morbidity and mortality.

The use of topical cyclosporine A 0.05% as treatment for primary alacrimia in Allgrove syndrome

Introduction: The purpose is to report a case on the use of cyclosporine A 0.05% for primary alacrimia in Allgrove syndrome or triple A syndrome (alacrimia, achalasia, and adrenal insufficiency). Case description: A 37-year-old man with achalasia treated surgically 11 years ago presented with sensation of a foreign body, irritation, and intermittent ocular redness for several years. Ophthalmological examination revealed bulbar hyperemia, Oxford grade 4 corneal staining, anisocoria, and optic atrophy. The patient was initially treated with washing with serum and lubricants. Due to the persistence of symptoms, treatment with cyclosporine A 0.05% was started observing a clinical improvement with a decrease in the symptoms caused by tear deficiency. Conclusion: It is important to emphasize the relevance of establishing an early diagnosis through a complete multidisciplinary clinical examination and a study of adrenal function. The treatment of dry eye in these patients is difficult to manage, with topical immunomodulators such as cyclosporine A as a good alternative when lubricants are insufficient. To our knowledge this is the first case of subjective and objective improvement of dry eye using cyclosporine A 0.05% in a case of alacrimia in triple A syndrome. Allgrove syndrome presentation does not always manifest with the classic triad and some symptoms may be not present at the time of diagnosis. Ophthalmologist and pediatrician should consider this syndrome in patients with symptoms as complex as lack of growth, crying without tears, and convulsions.