Discussion
In this case report, we described two twins diagnosed with AMES. Clinical, biochemical, and genetic data confirmed a congenital deficiency in the HSD11β2 enzyme (twin B). Usually, this syndrome is encountered early in the first decade of age. It is characterized by a set of symptoms such as high blood pressure, reduced renin and aldosterone levels, increased urine output and thirstiness, faltering growth, hypokalemia with metabolic alkalosis, and often a high level of calcium deposition in the kidneys. Cerebrovascular stroke is usually observed before age ten in undiagnosed, lately treated children [5–7]. Regarding inheritance of AMES, it is an AR (autosomal recessive) and caused by specific mutations. Homozygous/ compounds heterozygous or deletion mutations in a specific gene on chromosome 16 leads to the complete absence or significant decrease in the activity of the 11-b-HSD2 enzyme that produces cortisone from cortisol. The unprocessed active cortisol binds to its receptor, mineralocorticoid (MC) receptors, inducing the after-mentioned clinical features [8,9]. Our cases highlight many, if not all, of the features of the condition. Thus, in addition to the classical findings, they demonstrated a parent’s consanguinity, a strong suspicion of the affected twin, hypertensive retinopathy, and hypokalemic nephropathy.
These features have been reported in many other cases in the literature. Al-Harbi and Al-Shaikh reported three cases, two females and one male, with AMES, who presented with severe hypertension, low aldosterone, low renin levels, and hypokalemia. Genetic analysis confirmed the AMES diagnosis in these children. All cases had the typical clinical presentation of AMES, and their parents were first-degree cousins, considered consanguineous parents [10]. Yau et al. reported about a consanguineous Omani family with six AMES cases. Genetic analysis of affected family members confirmed a novel homozygous p.T267A mutation in HSD11B2. The diagnosis was confirmed with clinical signs and symptoms and biochemical investigations [11].
Azara et al. reported a consanguineous family from Iran with three affected cases. Two females and one male were diagnosed at 14, 11, and 4, respectively. At the time of presentation, low-renin hypertension, retinopathy, hypertrophy of the left ventricle, and mutation in R337C, within exon five of the 11ßHSD2’s gene, were found in this family with AMES [12]. The mainstay of treatment of our patients were potassium supplementations, thiazide (hydrochlorothiazide) and potassium sparing-diuretic (amiloride). We used thiazide diuretics to treat the nephrocalcinosis and associated hypercalciuria, while urine potassium loss could occur due to this drug; therefore, potassium supplementations were used. Amiloride was used as an alternative diuretic for thiazide if it was needed. Calcium channel blockers, dexamethasone, and other candidate treatments have been described in many cases with variable successes [13].