Tuberous Sclerosis, Type II Diabetes Mellitus and the PI3K/AKT/mTOR Signaling Pathways-Case Report and Literature Review

• Published in: Genes Vol. 14; no. 2; p. 433
• Main Authors: Jurca, Claudia Maria, Kozma, Kinga, Petchesi, Codruta Diana, Zaha, Dana Carmen, Magyar, Ioan, Munteanu, Mihai, Faur, Lucian, Jurca, Aurora, Bembea, Dan, Severin, Emilia, Jurca, Alexandru Daniel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Abdomen; AKT protein; Blood glucose; Brain cancer; Brain research; Carbamazepine; Care and treatment; Case Report; Case reports; Cell growth; Clonazepam; Convulsions & seizures; Determinism; Diabetes; Diabetes mellitus (non-insulin dependent); Diagnosis; Epilepsy; Genes; Genetic aspects; Glucose; Growth factors; hamartomas; Hemoglobin; Insulin resistance; Kinases; Laboratories; Literature reviews; Medical genetics; Metabolism; Metformin; Mutation; Physiological aspects; Proteins; Seizures; TOR protein; TSC1; TSC1 gene; TSC2; Tuberous sclerosis; Tumor suppressor genes; Tumors; Type 2 diabetes; type 2 diabetes mellitus; Romania; epilepsy; hamartomas; type 2 diabetes mellitus; TSC2; TSC1; Metformin; tuberous sclerosis
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes14020433

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous syndrome. It is manifested mainly in cutaneous lesions, epilepsy and the emergence of hamartomas in several tissues and organs. The disease sets in due to mutations in two tumor suppressor genes: and . The authors present the case of a 33-year-old female patient registered with the Bihor County Regional Center of Medical Genetics (RCMG) since 2021 with a TSC diagnosis. She was diagnosed with epilepsy at eight months old. At 18 years old she was diagnosed with tuberous sclerosis and was referred to the neurology department. Since 2013 she has been registered with the department for diabetes and nutritional diseases with a type 2 diabetes mellitus (T2DM) diagnosis. The clinical examination revealed: growth delay, obesity, facial angiofibromas, sebaceous adenomas, depigmented macules, papillomatous tumorlets in the thorax (bilateral) and neck, periungual fibroma in both lower limbs, frequent convulsive seizures; on a biological level, high glycemia and glycated hemoglobin levels. Brain MRI displayed a distinctive TS aspect with five bilateral hamartomatous subependymal nodules associating cortical/subcortical tubers with the frontal, temporal and occipital distribution. Molecular diagnosis showed a pathogenic variant in the TSC1 gene, exon 13, c.1270A>T (p. Arg424*). Current treatment targets diabetes (Metformin, Gliclazide and the GLP-1 analog semaglutide) and epilepsy (Carbamazepine and Clonazepam). This case report presents a rare association between type 2 diabetes mellitus and Tuberous Sclerosis Complex. We suggest that the diabetes medication Metformin may have positive effects on both the progression of the tumor associated with TSC and the seizures specific to TSC and we assume that the association of TSC and T2DM in the presented cases is accidental, as there are no similar cases reported in the literature.