Dados do Trabalho

Título

DEVELOPMENTAL DELAY ASSOCIATED WITH HYPOTONIA, PRESENTING WITH SIGNS OF SECOND NEURON IMPAIRMENT, AND ASSOCIATED WITH HEARING LOSS—A DIFFERENTIAL DIAGNOSIS.

Apresentação dos casos

A 6-year-old male patient presented at 3 months old, brought by his mother, with a history of motor delay, hypotonia, and inability to maintain trunk control. The mother reported a typical pregnancy and gestation, cesarean delivery without complications, and consanguineous parents (first cousins). At 6 months, the patient stopped interacting, followed by hypotonia and delayed dentition. Upon evaluation, the patient exhibited decreased muscle tone, reduced extensor plantar reflex, hypersalivation, nystagmus, hyperexcitability, malnutrition, spasticity, and clonus. Physical therapy, electroencephalogram, Brainstem Evoked Response Audiometry (BERA), and genetic testing were requested. The diagnosis of polyneuropathy and progressive leukoencephalopathy was confirmed, along with profound bilateral deafness identified via BERA. Genetic testing confirmed Sandhoff disease. The patient began treatment with prednisone and vigabatrin, which resulted in low clinical response, and was later switched to Depakene, currently showing good response to seizures

Discussão

Sandhoff disease is caused by mutations in the HEXB gene, located on chromosome 5. This gene provides instructions for the production of the enzyme beta-hexosaminidase, crucial for the proper functioning of nerve cells. In the presence of mutations in the HEXB gene, the HexB enzyme is produced in insufficient quantities. Consequently, there is an accumulation of glycosphingolipids in the cells of the central nervous system, particularly in neurons, leading to the characteristic neuronal degeneration seen in Sandhoff disease. Therefore, the mutation in the HEXB gene results in HexB enzyme deficiency, which causes the neurological and systemic symptoms observed in Sandhoff disease. There are different forms of presentation, with the infantile form being the most common and severe. Some symptoms include neuropsychomotor developmental delay, muscle spasticity, seizures, progressive loss of abilities, cerebral atrophy, deterioration of vision and hearing, feeding and swallowing difficulties, neurological dysfunction, cognitive impairment, among others.

Comentários finais

The severity and prevalence of systemic symptoms may vary among patients. Symptoms typically manifest in the first months of life and worsen over time. There is no cure, and treatments aim to alleviate symptoms and improve quality of life, focusing on symptom management, physical therapy, and occupational therapy.

Referências

Ramani PK, Sankaran BP. Tay-Sachs disease. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022.

Bibi F, Ullah A, Bourinaris T, Efthymiou S, Kriouile Y, Sultan T, et al. Tay-Sachs disease: Two novel rare HEXA mutations from Pakistan and Morocco. Klin Padiatr. 2021;233(5):226-30.

Zhang J, Chen H, Kornreich R, Yu C. Prenatal diagnosis of Tay-Sachs disease. Methods Mol Biol. 2019;1885:233-50.

Saouab R, Mahi M, Abilkacem R, Boumdin H, Chaouir S, Agader O, Amil T, Hanine A. A case report of Sandhoff Disease. Clin Neuroradiol. 2010; 21: 83-5.

Palavras Chave

Hypotonia; HEARING LOSS; MUTATIONS IN THE HEXH GENE