Case report

1. Case report Dr: REEM MURAD

2. Family 1 From Damascus

3. Case 1: Rasha A a 23 year old girl from Damascus She was admitted in our hospital with adrenal crisis She was diagnosed with gluococorticoid insufficiency at age 1 after a hypoglycemic seizure with low cortisol and elevated ACTH level and was discharged on oral glucocorticoids. Mineralocorticoid supplementation was initially instituted, but was subsequently discontinued. We started it again Pregnancy and birth history were unremarkable nasal speech at age 11

4. She had a history of dysphagia for food. A contrast swallow suggested esophageal achalasia. esophageal manometry and endoscopy confirmed achalasia. subsequently she underwent esophageal dilatations . with poor results We are preparing her for surgery

5. Review of systems was positive for crying without tears from early infancy Ophthalmologic evaluation and Schirmer test revealed alacrima. We started eye lubricants orbital imaging CT scan reveal atrophic lacrimal glands. During one-year follow-up, she developed ataxia

6. Case 2 Ablla.A is 14-year-old (sister of Rasha.A) She was diagnosed with gluococorticoid insufficiency at age 6 and she is on oral replasment therapy She had a history of recurrent pneumonitis requiring multiple hospital admissions. She also had dysphagia for solid food. a CT scan of the chest to investigate the cause of her recurrent pneumonitis: showed a hugely dilated esophagus with bilateral pneumonitis and was referred for further management. A contrast meal showed a dilated esophagus with smooth abrupt narrowing in the region of lower oesophageal sphincter suggestive of achalasia. The child underwent surgical correction which relieved her symptoms. After investigation she was also crying without tears

7. Family 2 From Raka

8. Case 3: Rabaa.A 10year old girl from Raka was referred to our endocrinology clinic for further follow up for short stature weight 20 kg height:116,5 cm (-3,1 SD). she was born at term. with unremarkable birth history .from consanguineous parents She was diagnosed with adrenal insufficiency at age 4 with( weakness , weight loss and darkening of skin). And started oral Hydrocortisone

9. She was complaining of extreme difficulties with swallowing, taking an hour to eat a meal, constant cough, inhalation of food. Achalasia was diagnosed on radiological and endoscopic findings and corrected surgically there was also no tears

10. Case 4-5-6 Ibraheem A - Maryam A - Abdullah A Brothers case 3 Same finding Their father refused to treat them

11. Case 7 Their brother died at age 5 undiagnosed

12. Discussion A diagnosis of Allgrove syndrome was made clinically, in all cases Allgrove syndrome ( Ttriple A Syndrome ) Alacrima Achalasia adrenal insufficiency

13. Allgrove (AAA) Syndrome In 1978 Allgrove and colleagues described 2 unrelated pairs of siblings with achalasia and ACTH insensivity, three had impaired lacrimation and one also had autonomic dysfunction. This triad achalasia adrenal insufficiency and alacrima became known as Ttriple A Syndrome

14. During the following years several reports in the literature have focused on more global autonomic disturbances associated with Allgrove syndrome leading to the name 4A syndrome adrenocortical insufficiency achalasia alacrima autonomic abnormalities

15. Frequency Incidence is unknown, and only scattered family and case reports are noted in the literature. The probable recurrence risk for future pregnancies from parents with a child affected with Allgrove syndrome is 25%.

16. Causes Inheritance is autosomal recessive and most patients have consanguineous parents Mutations in the AAAS gene, which encodes the product aladin, on chromosome 12q13 have been implicated as a cause of this disorder. which codes for a WD-repeat protein termed ALADIN

17. The pathology of this syndrome may be due to a progressive loss of cholinergic function throughout the body. The age of onset of symptoms is variable.

18. Clinical Presentation There is significant variability in the clinical Presentation Distinct facial appearance of Allgrove syndrome includes: long thin face with a long philtrum, narrow upper lip, down-turned mouth and microcephaly.

19. Glococorticosteroid deficiency is not apparent at birth The onset of adrenocortical impairment is usually before puberty, although preservation of cortisol secretion into the third decade has been reported

20. Neurological features Neurological features include hyperreflexia , dysarthria, muscle weakness ,nasal speech and mental retardation signs of autonomic dysregulation, decreased lacrimation, pupillary abnormalities, orthostatic hypotension, sexual impotence, disturbances of heart rate, and abnormal reactions to intradermal histamine Adults may exhibit progressive neural degeneration, develop parkinsonian features, and show mental deterioration.

21. Ophthalmic manifestations Ophthalmic manifestations : alacrima and keratoconjunctivitis sicca, sometimes resulting in corneal melt; lacrimal gland atrophy; pupillary abnormalities, including sluggish pupils, tonic pupils, and hypersensitivity to dilute miotics; and even optic atrophy. Patients with triple-A syndrome can present with accommodative dysregulation and ocular signs of autonomic dysfunction. Lacrimal gland CT scan may be helpful, and lacrimal gland biopsy may show neuronal degeneration associated with depletion of secretory granules in the acinar cell.

22. Skin examination Hyperpigmentation Hyperkeratosis and fine fissuring of the palms of the hands and soles of the feet represent a unique feature of this syndrome.

23. Mortality/Morbidity The most frequent initial presentation is a hypoglycemic seizure secondary to glucocorticoid deficiency. Most patients have previously unrecognized alacrima at the time of presentation. Achalasia leading to frequent vomiting or regurgitation also commonly occurs and may lead to growth failure The primary cause of mortality is unrecognized adrenal crisis.

24. Thank you