Case report: diagnostic challenges of Tay-Sachs disease

TT*Correspondence: [e-mail].

Abstract

Case Presentation: A.A.M.S, female, was born on 12/05/2017 in interior of Rio de Janeiro, diagnosed at age 4 with Tay-Sachs Disease (TSD). She began follow-up at the neuropediatrics service in Rio das Ostras, due to a complaint of behavior regression by family members at 1 year and 5 months, including social introspection, stereotypies, speech interruption, in addition to swallowing disorders, gait changes and an episode of generalized tonic-clonic seizure. The patient was born at 37 weeks and 6 days of gestational age with cesarean delivery. Mother without comorbidities with uneventful prenatal care. The patient was hospitalized with 15 days of life due to Upper Airway Infection. A.A.M.S was initially diagnosed with Autistic Spectrum Disorder (ASD) at the age of 2, with Brainstem Audiometry and imaging tests initially unchanged. She was referred to the genetics service in Rio de Janeiro, the karyotype and CGH-array were requested, with normal results. The exome sequence was subsequently ordered and confirmed the presence in homozygosis of the variant NM_000520.6(Hexosaminidase):c.533G>A;p.(Arg178His), related to TSD variant B1.

Discussion: Tay-Sachs is a hereditary autosomal recessive and progressive disease. In most cases it has no manifestations at birth, it presents adult, juvenile and infantile forms, whose initial symptoms appear at 3 to 6 months and may present with myoclonus or loss of motor function at 10 months with loss of contact eyesight, irritability, and apathy. It is caused by mutation in the alpha subunit of the gene HEXA, identified on chromosome 15q23-q244, which generates a lysosomal accumulation of ganglioside GM2 in neuronal cells. The diagnosis can be suspected through amniocentesis or chorionic villus sampling and confirmed by molecular tests. Its differential diagnosis is ASD in the initial manifestations. Treatment of TSD consists of supporting clinical manifestations and managing intercurrences and infectious diseases with proper maintenance of nutrition, in addition to seizure control and multidisciplinary follow-up. Patients with infantile form usually die by the age of 4 to 5 years. Death usually results from recurrent infections.

Final Comments: The present case emphasizes the discussion of the diagnostic difficulty of a rare, serious, and hereditary disease due to the technology used for its discovery being available only in large centers, in addition to the nonspecific initial manifestations corroborating the lack of suspicion of the disease.

Publication History

Article published online:
12 May 2025