Doença de Tay-Sachs: relato de caso / Tay-Sachs disease: a case report

RESUMO A doença de Tay-Sachs é um distúrbio neurodegenerativo autossômico recessivo, o qual envolve o metabolismo dos lipídios, levando ao acúmulo de gangliosídeos nos tecidos, devido à deficiência da enzima hexosaminidase A. Esse depósito progressivo resulta em perda da função neurológica e, quando acomete as células ganglionares da mácula, causa o achado típico da doença, a "mácula em cereja". A patologia é diagnosticada por meio dos níveis de hexosaminidase A e hexosaminidase total no soro, além análise do DNA do gene HEXA. Este caso relata uma criança com doença de Tay-Sachs cujo diagnóstico foi suspeitado por conta dos achados oftalmológicos.

ABSTRACT Tay-Sachs Disease is an autosomal recessive neurodegenerative disorder, which involves the metabolism of lipids, leading to the accumulation of gangliosides in the tissues, due to the deficiency of the enzyme Hexosaminidase A. This progressive deposit results in loss of neurological function and, when it affects macula ganglion cells, it causes the typical disease finding, the "cherry red spot". The pathology is diagnosed through the levels of Hex A and total Hexosaminidase in the serum, in addition to the analysis of the DNA of the HEXA gene. This case reports a child with Tay-Sachs disease with a suspected diagnosis was through ophthalmologic findings.

Enfermedad de Tay-Sachs / Tay-Sachs disease

La enfermedad de Tay-Sachs es un trastorno neurodegenerativo progresivo de herencia autosómica recesiva. Se debe a la deficiencia de la enzima β-hexosaminidasa A, que provoca una acumulación de gangliósidos GM2 en los lisosomas. Se incluye dentro de las esfingolipidosis. De las esfingolipidosis que presentan mancha rojo cereza en la mácula, la enfermedad de Tay-Sachs es la única en la que no se evidencia hepatoesplenomegalia. La variante más frecuente se inicia en la lactancia. Se presenta un lactante del sexo masculino al que se le realizó el diagnóstico de esta entidad a los 8 meses de edad. A partir de los 4 meses comenzó a presentar una reacción de sobresalto. A los 6 meses comenzó a perder habilidades previamente adquiridas y crisis epilépticas mioclónicas. Se constató una disminución de la actividad específica de la enzima hexosaminidasa A en leucocitos.

Tay-Sachs disease is a progressive autosomal recessive inherited neurodegenerative disorder caused by Beta-hexosaminidase A enzyme deficiency that in turn provokes GM2 ganglioside accumulation in the lysosomes. It is included in the sphyngolipidoses classification. Among the sphyngolipidoses that present with cherry-red spot in the macula, Tay-Sachs disease is the only one that does not show hepatosplenomegaly. The most frequent variant begins at the breast-feeding phase. This report presented a male nursling who was diagnosed with Tay-Sachs disease at the age of 8 months. At 4 months of age, he had begun getting some fright reactions. At 6 months-old, he began losing his previously acquired skills and suffering myoclonic seizures. The cause was the reduced specific activity of the hexosaminidase A enzyme in leukocytes.

Molecular cloning, sequence identification and tissue expression profile of three novel sheep (Ovis aries) genes - BCKDHA, NAGA and HEXA

The complete coding sequences of three sheep genes- BCKDHA, NAGA and HEXA were amplified using the reverse transcriptase polymerase chain reaction (RT-PCR), based on the conserved sequence information of the mouse or other mammals. The nucleotide sequences of these three genes revealed that the sheep BCKDHA gene encodes a protein of 313 amino acids which has high homology with the BCKDHA gene that encodes a protein of 447 amino acids that has high homology with the Branched chain keto acid dehydrogenase El, alpha polypeptide (BCKDHA) of five species chimpanzee (93 percent), human (96 percent), crab-eating macaque (93 percent), bovine (98 percent) and mouse (91 percent). The sheep NAGA gene encodes a protein of 411 amino acids that has high homology with the alpha-N-acetylgalactosaminidase (NAGA) of five species human (85 percent), bovine (94 percent), mouse (91 percent), rat (83 percent) and chicken (74 percent). The sheep HEXA gene encodes a protein of 529 amino acids that has high homology with the hexosaminidase A(HEXA) of five species bovine (98 percent), human (84 percent), Bornean orangután (84 percent), rat (80 percent) and mouse (81 percent). Finally these three novel sheep genes were assigned to GenelDs: 100145857, 100145858 and 100145856. The phylogenetic tree analysis revealed that the sheep BCKDHA, NAGA, and HEXA all have closer genetic relationships to the BCKDHA, NAGA, and HEXA of bovine. Tissue expression profile analysis was also carried out and results revealed that sheep BCKDHA, NAGA and HEXA genes were differentially expressed in tissues including muscle, heart, liver, fat, kidney, lung, small and large intestine. Our experiment is the first to establish the primary foundation for further research on these three sheep genes.