A broad range of symptoms in allgrove syndrome: single center experience in Southeast Anatolia.

BACKGROUND: Allgrove syndrome (OMIM 231550) is a rare autosomal recessive disease characterized by non-CAH primary adrenal insufficiency (non-CAH PAI), alacrima, and achalasia. It is caused by mutations in the AAAS gene. The syndrome is also associated with variable progressive neurological impairment and dermatological abnormalities. METHODS AND RESULTS: We diagnosed 23 patients from 14 families with Allgrove syndrome, based on the presence of at least two characteristic symptoms, usually adrenal insufficiency and alacrima, between 2008 and 2018. A previously described nonsense variant of AAAS was detected in 19 patients from 12 families at homozygous state. Another novel homozygous mutation (c.394-397delCTGT) in AAAS was detected in four patients from two families. Presenting symptoms were alacrima (23/23; 100%), adrenal insufficiency (18/23; 78%), achalasia (13/23; 57%), short stature/growth retardation (16/23; 70%), hyperreflexia (15/23; 65%), palmoplantar hyperkeratosis (13/23; 57%), hyperpigmentation of the skin (10/23; 43%), hypoglycemia-induced convulsion (7/23; 30%), swallowing difficulty and vomiting (6/23; 26%). Serum DHEAS concentrations were low in all patients (23/23; 100%). CONCLUSIONS: Clinical symptoms vary even among patients carrying the same mutation. Triple A syndrome should be considered in the etiology of non-CAH PAI in Arab populations and in Southeast Turkey. Any child with non-CAH PAI should be evaluated for the presence of alacrima and/or achalasia or family history of alacrima and/or achalasia. Children with alacrima and/or achalasia should also be investigated for adrenal insufficiency. Definitive molecular diagnosis is essential for early diagnosis and management of adrenal insufficiency, neurological symptoms, and growth retardation in patients and early diagnosis of as yet asymptomatic cases in the family, together with genetic counseling.

Relative hypoaldosteronism in a patient with Wolcott-Rallison syndrome.

BACKGROUND: Wolcott-Rallison syndrome is an autosomal recessive, multisystem disorder with onset of diabetes in the neonatal period or early infancy. CASE REPORT: A 9-year-old girl with diabetes and growth failure from 2 months of age presented with ketoacidosis and multiple organ failure. Evaluation for short stature revealed epiphyseal dysplasia. A homozygous mutation in the EIF2AK3 gene confirmed the clinical diagnosis of Wolcott-Rallison syndrome. She was euthyroid. Biochemical evaluation for potential adrenal dysfunction because of persistently elevated serum potassium (range 5.9-6.3 meq/l) and low serum sodium levels (range 128-130 meq/l) 2 weeks after resolution of ketoacidosis yielded normal findings with respect to basal corticotropin (31 pg/ml) and cortisol (18.7 µg/dl) levels. Estimated GFR-Schwartz (36.9 ml/min/1.73 m(2) ) was consistent with stage 3 chronic renal failure. The transtubular potassium gradient was 1.39 (normal value in hyperkalemic states: > 4.1). The plasma aldosterone (upright: 241.3 pmol/l) was within normal ranges, and plasma renin [39 pg/ml (range 5.41-34.53 pg/ml)] was slightly elevated. The patient was diagnosed as having relative hypoaldosteronism and was started on a sodium-rich diet and low potassium. Failure to respond to the dietary intervention prompted a trial of oral fludrocortisone with subsequent normalization of electrolyte levels. CONCLUSIONS: This is the first case report of Wolcott-Rallison syndrome complicated with relative hypoaldosteronism. Further research is needed to probe the causal inference of relative hypoaldosteronism with chronic renal failure in patients with Wolcott-Rallison syndrome.