IMPE Abstracts

Background: Autoimmune polyglandular syndromes are rare in children. APS-1 typically presents in childhood and adolescence, is due to mutation in AIRE gene. APS-2 typically presents in adolescence and adulthood, is polygenic in nature. Myasthenia gravis is an autoimmune disorder characterized by neuromuscular weakness, fatigue, due to autoantibodies toward acetylcholine receptor. The association of myasthenia gravis with other autoimmune diseases is well known, but it rarely occurs in young children.

Objectives: To describe a rare case where a child was diagnosed with severe autoimmune hypothyroidism, Addison disease, myasthenia gravis at age 4 years.

Methods: A 4-year-old Caucasian female presented with few days history of gastroenteritis, poor oral intake, seizures in face of severe low glucose 13 mg/dl. Was found to have elevated TSH= 60.9 UIU/ml (reference 0.3-4.5), low fT4=0.59 ng/ml (reference 0.89-1.7), low am cortisol level 2.6 mg/dl. History revealed that patient has had low stamina, fatigue for years. At the time of diagnosis significant darkening of the skin, facial edema and hypotonia were noticed on physical exam. Patient was also noticed to have gross motor skills delays. Subsequent tests demonstrated highly elevated ACTH >2,000 pg/ml (reference 7.2-63.3). Thyroid Peroxidase antibodies elevated 176 IU/ml (reference 0-13). ACTH stim test showed baseline cortisol 0.72 mg/dl, 30 min cortisol 0.92 u/dl, 60 min cortisol 0.7 mg/dl. Patient was started on levothyroxine, hydrocortisone. She was found to have elevated ACHR blocking antibodies = 43% (reference 0-25%) and diagnosed with myasthenia gravis. Was started on pyridostigmine and demonstrated clinical improvement in neuromuscular symptoms. Genetic testing for AIRE gene was negative. After treatment was initiated, patient made a significant progress in her motor skills development, energy level normalized. Skin color became less dark. Muscle tone improved. Repeated bloodtests: TSH=2.9 UIU/ml (reference 0.67-4.16), fT4=1.21 ng/dl (reference 0.89-1.76), ACTH=329 pg/ml (reference 7.2-63.3).

Results: This is a case report of a rare incidence of severe autoimmune hypothyroidism, severe adrenal insufficiency Addison disease, myasthenia gravis in a young child.

Conclusion: Autoimmune polyglandular syndromes are rare in children. Although presence of one autoimmune condition makes patients to be more predisposed to develop others is well known, the association of Addison disease, autoimmune thyroid disease and myasthenia gravis in very young child is extremely rare and not very well described in the literature. Autoimmune illnesses should be suspected even in very young children with recurrent illnesses, fatigue, developmental delays.

Conclusion: This analysis of published literature supports the concept that individuals with heterozygous or biallelic variants in the MC4R pathway (POMC, PCSK1, LEPR, NCOA1, and SH2B1) share many common clinical characteristics related to early-onset obesity and hunger, as well as obesity-associated comorbidities.