Allgrove syndrome: a case report

Allgrove syndrome is an autosomal recessive disease which is characterized by Achalasia, Alacrimia and ACTH-resistant Adrenal deficiency with progressive neurological manifestations. Allgrove syndrome is caused due to mutations in AAAS gene, localized on chromosome 12q13. This report relates to an 8 years old female child who had complaints of vomting, fever, cough, hyperpigmentation and poor weight gain. Barium swallow, ophthalmic examination and ACTH stimulation test proves that patient has Allgrove’s syndrome. Management consisted of initiation of cortisone therapy which was successful in improving the hyper pigmentation. Patient was planned for surgical intervention for achalasia cardia on follow-up. Allgrove’s syndrome may be an under diagnosed disorder. High index of suspicion is needed when patients present with such complex symptoms. Diagnosing and timely intervention helps in reducing the morbidity and mortality.

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.

SAT-219 Allgrove Syndrome: How to Suspect a Problem?

Background: Allgrove syndrome (triple A syndrome) is a rare autosomal recessive multisystem disease characterized by adrenal insufficiency, alacrimia and achalasia. It is caused by a mutation in the AAAS gene (12q13) encoding the protein ALADIN (1). This syndrome is often associated with neurological dysfunction disorders, amyotrophy, in such cases, it is named 4A and 5A syndrome, but sometimes there is also 2A syndrome. Prevalence:<1/1000000. The first description was in 1978. Clinical case: A 18-year patient A. complained of fatigue, weakness, darkening of the skin. From anamnesis of life: born from the first pregnancy without complications, weight 3200g. Parents often turned to the pediatrician with complaints: lethargy, frequent regurgitation, ARVI up to 6–7 times a year. Slow weight gain, dyspeptic syndrome (nausea, vomiting) was noted objectively. At the age of 3, the boy entered the surgical department with acute abdomen, fever, vomiting. Achalasia was revealed, reconstructive surgery was carried out. In the diagnostic search for the causes of body weight loss he was directed to the endocrinologist. There were an increase in ACTH 470 pg/ml (0,0-46 pg/ml), cortisol 0.05 µg/DL. Diagnosis: primary chronic adrenal insufficiency; the dose of hydrocortisone 10 mg/day did not change with age. An in-depth anamnesis found: the patient never cried with tears. Objectively: asthenic body type, BMI 16.5 kg/m2, hyperpigmentation of the palms, armpits; weakness in the proximal muscles of the limbs. Laboratory studies: ACTH 95 PG/ml, cortisol 0.1 µg/DL (3.7–19.4 µg/DL). The secretion of mineralocorticoids was evaluated: plasma aldosterone and renin levels were within the reference values. Ophthalmologist: injected conjunctiva, sclera. Schirmer’s test: mild alacrimia. It allowed to make the diagnosis: “Primary chronic adrenal insufficiency. Condition after surgery for achalasia (1997). Alacrimia. Allgrove Syndrome.” The dose of hydrocortisone was increased to 17.5 mg/day. In 2019, the patient complained of a sharp deterioration of health, darkening of the skin. The dose of hydrocortisone was increased to 25 mg/day (15 mg at 8.00, 10 mg in the afternoon). The ophthalmologist noted an increase in the severity of alacrimia, artificial tear drops was recommended. The diagnosis was confirmed by pathogenic mutation c.43C>T of the AAAS gene. Discussion: Despite the full clinical picture, the right diagnosis was made only after 14 years. We shown the difficulty of diagnosis is due to the lack of awareness of clinicians about the disease, the importance of interdisciplinary interaction, as well as the need for follow-up of such patients. Reference: (1) Handschug K, Sperling S, Yoon SJ, et al. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Human Molecular Genetics. 2001;10:283–290.

Allgrove syndrome and motor neuron disease

Allgrove or triple A syndrome (AS or AAA) is a rare autosomal recessive syndrome with variable phenotype due to mutations in AAAS gene which encodes a protein called ALADIN. Generally, it’s characterized by of adrenal insufficiency in consequence of adrenocorticotropic hormone (ACTH) resistance, besides of achalasia, and alacrimia. Neurologic features are varied and have been the subject of several case reports and reviews. A few cases of Allgrove syndrome with motor neuron disease have been already described. A 25-year-old white man, at the age of four, presented slowly progressive distal amyotrophy and weakness, autonomic dysfunction, dysphagia and lack of tears. He suffered later of orthostatic hypotension and erectile dysfunction. He presented distal amytrophy in four limbs, tongue myofasiculations, alacrimia, hoarseness and dysphagia due to achalasia. The ENMG showed generalized denervation with normal conduction velocities. Genetic testing revealed 2 known pathogenic variants in the AAAS gene (c.938T>C and c.1144_1147delTCTG). Our case presented a distal spinal amyotrophy with slow evolution and symptoms and signs of AS with a mutation in AAAS gen. Some cases of motor neuron disease, as ours, may be due to AAS. Early diagnosis is extremely important for symptomatic treatment.