Endocrine Abstracts

Introduction: Glycogen storage disease type Ia is a rare genetic disorder that develops due to deficient activity of the enzyme glucose 6-phosphatase and manifests clinically early in life with hypoglycemia and failure to thrive, as well as with organ dysfunction, due to excess glycogen accumulation, including hepatomegaly and kidney dysfunction. Endocrine manifestations are commonly encountered in these patients. However, due to their rarity, endocrine dysfunction has not been well-acknowledged and studied.

Case presentation: A 17-year old girl with glycogen storage disease type Ia diagnosed in neonatal life, presented with oligomenorrhea since menarche (14 years of age). Clinical examination revealed a normally grown girl, Tanner Stage V, with BMI=24.2 kg/m² and normal blood pressure (120/70 mmHg). No signs of hyperandrogenism or acanthosis nigricans were noticed. A full hormonal workup revealed normal thyroid function, increased LH/FSH ratio, normal testosterone and elevated levels of 17-OH progesterone (17-OH prog=5.04 ng/ml). Additionally, the patient displayed elevated levels of aldosterone, with suppressed plasma renin activity, leading to an aldosterone-to-renin ratio of 36. Due to the above findings, the patient was submitted to adrenocorticotropic hormone (ACTH) stimulation test, which showed adequate excretion of cortisol, along with increased levels of 17-OH progesterone and androstenedione following stimulation. The renin-aldosterone axis was further assessed with IV saline infusion test, which, however, was not diagnostic due to technical difficulties. In a 24-hour urine collection, an increased excretion of potassium, with normal potassium levels in the plasma, was noticed. Consequently, due to the possibility of a non-typical form of congenital adrenal hyperplasia (NCAH) and a coexisting subclinical hyperaldosteronism, genetic testing to analyze both CYP21A and CYP11B1 genes from genomic DNA of the patient was undertaken. The molecular testing results revealed 4 variations in homozygosity and 1 in heterozygosity at the CYP21A2 gene, as well as 1 variation in heterozygosity at the CYP11B1 gene, which, however, are not reported in all databases reviewed and their clinical significance remains unknown. The results of genetic testing of both parents, which will illuminate further this case, are pending.

Conclusions: The clinical and hormonal phenotype of NCAH in a girl with glycogen storage disease type 1A, in combination with a genomic analysis revealing mutations in both CYP21A2 and CYP11B1 genes, pose a question whether there is a novel link between these two clinical entities.