|Year : 2021 | Volume
| Issue : 3 | Page : 283-285
Diagnostic and therapeutic dilemmas in alacrima, achalasia, and addisonism syndrome
Laavanayaa Somasundaram, Suhas Prabhakar
Department of Ophthalmology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
|Date of Submission||15-Dec-2020|
|Date of Decision||09-Jun-2021|
|Date of Acceptance||25-Jun-2021|
|Date of Web Publication||09-Sep-2021|
Prof. Suhas Prabhakar
Department of Ophthalmology, Sri Ramachandra Institute of Higher Education and Research, No. 1, Ramachandra Nagar, Porur, Chennai - 600 116, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Allgrove's syndrome is a rare genetic disorder characterized by alacrima, achalasia, and addisonism (AAA syndrome). The rarity of the disease and the requirement of genetic analysis to confirm the disease cause diagnostic issues. The variable nature of presentation of the classical triad is known. Requirement of education among the clinician and parents is essential to avoid severe or fatal complications. We present a case of male child who presented with near-fatal hypoglycemia and on evaluation found to have early-onset complete manifestation of AAA syndrome. The case also highlights the need of periodical assessment, awareness among clinicians about disease, and parental education to avoid severe complications.
Keywords: Addisonism, alacrima, allgrove
|How to cite this article:|
Somasundaram L, Prabhakar S. Diagnostic and therapeutic dilemmas in alacrima, achalasia, and addisonism syndrome. TNOA J Ophthalmic Sci Res 2021;59:283-5
|How to cite this URL:|
Somasundaram L, Prabhakar S. Diagnostic and therapeutic dilemmas in alacrima, achalasia, and addisonism syndrome. TNOA J Ophthalmic Sci Res [serial online] 2021 [cited 2021 Sep 26];59:283-5. Available from: https://www.tnoajosr.com/text.asp?2021/59/3/283/325726
| Introduction|| |
Allgrove's syndrome (alacrima, achalasia, and addisonism [AAA] syndrome) is a rare genetic disorder characterized by alacrima, achalasia, and addisonism. The autosomal recessive condition has a median age of presentation of 5 years with the prevalence of alacrima, achalasia, and addisonism of 93.2%, 90.1%, and 79.4%, respectively. Although they do not follow specific order, alacrima is usually the first manifestation to be noted by the parents and achalasia has a delayed onset at 10 years of age. Adrenal insufficiency manifests at a median age of 6 years with varying presentation including life-threatening hypoglycemia., We present a case of male child who presented with near-fatal hypoglycemia and on evaluation found to have early-onset complete manifestation of AAA syndrome.
| Case Report|| |
Male child presented at 3 years 6 months with complaints of generalized tonic–clonic seizures followed by loss of consciousness. Parents also gave a history of failure to thrive and generalized hyperpigmentation. He is the first child born of second-degree consanguineous marriage with no significant family history. Clinical examination revealed bilateral epicanthic fold, left cryptorchidism, and perioral hyperpigmentation [Figure 1]. Neurological examination was normal though he gave a history of multiple episodes of seizures. Initial workup showed hypoglycemia. Provisional diagnosis of adrenal insufficiency was made with seizures secondary to recurrent hypoglycemia. Adrenal antibody was negative, and computed tomography of the abdomen and brain was normal. Low insulin-like growth factor 1 levels and positive clonidine stimulation test were suggestive of growth hormone deficiency. However, high adrenocorticotropic hormone (ACTH) levels, positive ACTH stimulation test, and growth improvement with trial steroids indicated primary addisonism. Schimer test was positive (5 mm in both eyes at the end of 5 min) [Figure 2]. Barium swallow was normal. The child was started on steroid supplementation and tear supplementation. The patient showed clinical improvement with gain in weight at 6 months of follow-up. He was lost to follow-up and presented 3 years later with a 6-month history of dysphagia and loss of weight (>20% in 6 months). Barium swallow was suggestive of achalasia cardia [Figure 3]a and [Figure 3]b. Esophageal manometry showed panesophageal measurement with absent lower esophageal sphincter relaxation [Figure 4]. Diagnosis of type 2 achalasia cardia was made. Pneumatic dilatation was performed resulting in significant improvement in clinical symptoms. The child started gaining weight. At 8 years of age, the child is on tear supplementation and steroids and is doing well.
|Figure 1: Photopanel showing perioral hyperpigmentation (a), hyperpigmented knuckles (b), bilateral epicanthic folds (c and d)|
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|Figure 2: Schirmer test-positive: (a) <1 mm in both eyes at the end of 2 min; (b) 5 mm in both eyes at the end of 5 min|
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|Figure 3: Barium swallow (a) Anteroposterior view and (b) lateral view showing dilated esophagus with smooth tapering at the lower end of esophagus and persistent hold up of contrast|
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|Figure 4: High-resolution esophageal manometry showing panesophageal measurement with absent lower esophageal sphincter relaxation. Median integrated relaxation pressure was high|
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| Discussion|| |
Allgrove's syndrome is a rare autosomal recessive disorder characterized by alacrima, adrenal insufficiency, and achalasia cardia. Often, autonomic dysfunction and neurodegeneration are found along with the above-mentioned pathologies. The disease is a resultant of mutation involving the gene that codes for the protein ALADIN (alacrima, achalasia, adrenal insufficiency, neurological disorder) located on the chromosome 12q13. Literature evidence of the disease is severely hampered by the rarity of the disease and diagnostic difficulty.
Alacrima is the most common and earliest manifested component of the disorder. It is often noticed by the parents by the lack of tears in the child from birth or 1st year of life., Adrenal insufficiency is usually the next common component and usually occurs <3 years of life. Adrenal function can be deficient, insufficient, or compensated. Depending on the status, the child can present with hypoglycemia and seizures or can be asymptomatic because of the compensated nature of adrenal function. Apart from glucocorticoid insufficiency, the child can have also deficiency of mineralocorticoid and/or sex hormone. Achalasia cardia is the last of triad to manifest and is the most variable in the timing of presentation.
The rarity of the disease and the requirement of genetic analysis to confirm the disease cause diagnostic issues. The variable nature of presentation of the classical triad is known. No genotype–phenotype correlations have been reported indicating the incomplete understanding the disease. Diagnosing child with all three components can make diagnosis easier. However, if there is absence of one at the time of diagnosis it might indicate two possibilities. The first is phenotypic variation of the disease and the other can be delayed presentation of one of the components of AA syndrome, typically achalasia cardia, at a later part of life. In such doubtful scenarios, genetic analysis can confirm the diagnosis.
Treatment of the condition is symptom based. Alacrima is managed with tear supplementation and management of dry eye-related complication if already occurred. Patients with compensated adrenal function should be informed and educated to manage a glucocorticoid replacement therapy in case of stressful conditions, with no need for systematic long-term treatment. Achalasia cardia is typically managed with calcium channel blockers and pneumatic dilatation in mild and severe cases. In the third decade of life, peroral esophageal myotomy or surgical esophageal myotomy can be offered as long-term management option.
The case highlights the requirement of education among the clinicians and parents to avoid severe or fatal complications. Although alacrima is often noted by parents at birth or during neonatal period, the diagnosis of allgrove's syndrome is often made after manifestation of severe forms of other two components of the disease, namely adrenal insufficiency and achalasia cardia. Near-fatal hypoglycemia occurring due to adrenal insufficiency can be averted if alacrima was diagnosed and evaluated appropriately. Similarly, in our case, periodical assessment and parental education could have avoided the weight loss secondary to achalasia cardia.
| Conclusion|| |
Allgrove's syndrome is rare and should be considered in every child with alacrima. Wide spectrum of the clinical presentation of allgrove's syndrome reflects the pleiotropic nature of underlying genetic mutation. Early diagnosis of allgrove's syndrome is crucial as it prevents unnecessary investigations and inappropriate treatment. Periodical assessment of the disease components and their severity will help in preventing serious consequences.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Patt H, Koehler K, Lodha S, Jadhav S, Yerawar C, Huebner A, et al.
Phenotype-genotype spectrum of AAA syndrome from Western India and systematic review of literature. Endocr Connect 2017;6:901-13.
Singh K, Puri RD, Bhai P, Arya AD, Chawla G, Saxena R, et al.
Clinical heterogeneity and molecular profile of triple A syndrome: A study of seven cases. J Pediatr Endocrinol Metab 2018;31:799-807.
Kurnaz E, Duminuco P, Aycan Z, Savaş-Erdeve Ş, Muratoğlu Şahin N, Keskin M, et al.
Clinical and genetic characterisation of a series of patients with triple A syndrome. Eur J Pediatr 2018;177:363-9.
Dumic M, Barišic N, Kusec V, Stingl K, Skegro M, Stanimirovic A, et al.
Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome. Eur J Pediatr 2012;171:1453-9.
Milenkovic T, Zdravkovic D, Savic N, Todorovic S, Mitrovic K, Koehler K, et al.
Triple A syndrome: 32 years experience of a single centre (1977-2008). Eur J Pediatr 2010;169:1323-8.
Roucher-Boulez F, Brac de la Perriere A, Jacquez A, Chau D, Guignat L, Vial C, et al.
Triple-A syndrome: A wide spectrum of adrenal dysfunction. Eur J Endocrinol 2018;178:199-207.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]