Case report: mitochondrial DNA depletion syndrome 2

*Correspondence: [e-mail].

Abstract

Case Presentation: E.F.C.S., 2 years old, male, first child of the couple, sought our service when was 1 year and 5 months old due to regression of motor milestones from 1 year of age, which until then were age-appropriate. They denied consanguinity or similar family history. On examination, the patient presented global hypotonia, hyporeflexia, little voluntary movement, and no other alterations. Molecular research was done, positive for mitochondrial DNA depletion syndrome 2. Currently the patient is under gastrostomy, tachyostomy and multidisciplinary supervision.

Discussion: Mitochondrial DNA depletion syndrome 2 or mitochondrial DNA depletion myopathy related to mitochondrial thymidine kinase (TK2) is a compound homozygous or heterozygous mutation in the TK2 gene on chromosome 16q21, has autosomal recessive inheritance, and may present with great clinical variability, from childhood onset with a rapidly progressive course with early death due to respiratory failure or late onset with slowly progressive myopathy. It mainly involves the genes H90N, I181N, H163N, I254N. The onset is usually near the age of 2 years. Among the clinical characteristics found, we have facial diplegia, hypotony, external ophthalmoplegia, myopathic stand up, diffuse muscular atrophy, delay or regression in the acquisition of motor skills, generally evolving to respiratory failure due to muscular weakness. Among the complementary exams we can observe lactic acidosis, aminoaciduria, increase of creatine kinase, electroneuromyography with myopathic alterations and muscle biopsy with torn red fibers. The diagnosis is made through molecular research.

Final Comments: This case emphasizes the importance of diagnostic suspicion for better follow-up and early referral to a geneticist for genetic counseling.

Publication History

Article published online:
12 May 2025