Background: Ring chromosome 18 [r18] is a rare constitutional chromosomal aberration syndrome, characterized by dysmorphic face, hypoactivity, short stature, and delayed development. Autoimmune thyroiditis and immunoglobulin (Ig) A deficiency are occasionally associated with chromosome-18 deletion syndromes.
Summary: Here, we report a 2-year-old male child with r(18) syndrome and a selective IgA deficiency (<1.6 mg/dL, reference range [rr]: 20-149), who developed hypothyroidism and liver dysfunction. Thyroid function tests (thyroid-stimulating hormone [TSH]: 1031 μIU/mL, rr 0.43-4.0; free triiodothyronine: 0.52 pg/mL, rr 2.37-4.65; free thyroxine: 0.11 ng/dL, rr 1.03-2.00) and positive thyroid antibodies (anti-TSH receptor 1.7 IU/L, cut-off index [coi]: <1.0, antithyroid peroxidase 171 IU/mL, coi <0.3, and antithyroglobulin 2.8 IU/mL, coi <0.3) indicated autoimmune hypothyroidism. Elevated levels of aspartate aminotransferase (AST, 240 IU/L, rr 17-39) and alanine aminotransferase (ALT, 315 IU/L, rr 4-23), but negative antibodies against LKM and mitochondrial M2, suggested no autoimmune hepatitis. Transaminase levels became normalized after he was given levothyroxine therapy to achieve the euthyroid state, but they repeatedly became elevated when levothyroxine was inadvertently discontinued (peak AST=409 IU/L; peak ALT=390 IU/L). A maintenance dose of levothyroxine has effectively maintained the euthyroid state and normalized liver function tests despite no immunosuppressive therapy.
Conclusions: The r18 patient with autoimmune hypothyroidism and IgA deficiency suffered from idiopathic hepatitis. The liver dysfunction was associated with hypothyroidism that resolved with thyroid hormone treatment. While the former combination has been described, the latter has not. The reason for the development of hepatitis in association with hypothyroidism is unexplained. However, we postulate that it might be related, in ways that are not clear, to the deleted genes of r18.