RESUMO
The human genome encodes a gene for an enzymatically active chitinase (CHIT1) located in a single copy on Chromosome 1, which is highly expressed by activated macrophages and in other cells of the innate immune response. Several dysfunctional mutations are known in CHIT1, including a 24-bp duplication in Exon 10 causing catalytic deficiency. This duplication is a common variant conserved in many human populations, except in West and South Africans. Thus it has been proposed that human migration out of Africa and the consequent reduction of exposure to chitin from environmental factors may have enabled the conservation of dysfunctional mutations in human chitinases. Our data obtained from 85 indigenous Amerindians from Peru, representative of populations characterized by high prevalence of chitin-bearing enteroparasites and intense entomophagy, reveal a very high frequency of the 24-bp duplication (47.06%), and of other single nucleotide polymorphisms which are known to partially affect enzymatic activity (G102S: 42.7% and A442G/V: 25.5%). Our finding is in line with a founder effect, but appears to confute our previous hypothesis of a protective role against parasite infection and sustains the discussion on the redundancy of chitinolytic function.
Assuntos
Quitina/química , Hexosaminidases/genética , Imunidade Inata/genética , Animais , Quitina/genética , Dieta , Hexosaminidases/deficiência , Humanos , Indígenas Sul-Americanos , Macrófagos/metabolismo , Macrófagos/parasitologia , Mutação , Parasitos/química , Parasitos/metabolismo , Peru , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Hexosaminidases/deficiência , Adolescente , Adulto , África/etnologia , Alelos , Ásia/etnologia , Brasil/epidemiologia , Cromossomos Humanos Par 1/genética , Etnicidade/genética , Europa (Continente)/etnologia , Feminino , Duplicação Gênica , Frequência do Gene , Genótipo , Hexosaminidases/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Two additional patients with alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency are described. An 11-month-old girl with nonconsanguineous parents had generalized seizures and no angiokeratoma. Biochemical investigation showed persistent slight oligosacchariduria; enzymatic analysis of plasma, leukocytes, and fibroblasts revealed profound alpha-NAGA deficiency. Heterozygote enzyme levels were found in both parents. The mother has epilepsy, and epilepsy is present in the father's family. A younger, clinically healthy brother also had the enzyme deficiency. Electron microscopy of lymphocytes from the index patient showed no vacuolization. Incubation of cultured fibroblasts with Helix pomatia lectin showed the presence of intracellular N-acetylgalactosamine-containing storage material, not present in a series of 12 normal fibroblast lines. Our cases cannot be classified definitely as infantile cases. Biochemically the diagnosis could easily have been missed. Urinary oligosaccharide pattern after resorcinol staining was identical to those previously described, but excretion was significantly lower than in the reported infantile cases and the bands disappeared after the urine was desalted. The enzyme defect in leukocytes would have been missed with one of the commercial substrates used. For this mild variant of alpha-NAGA deficiency, the clinical pattern is not yet clear; a longer follow-up period is needed.
Assuntos
Hexosaminidases/deficiência , Diagnóstico Diferencial , Doenças em Gêmeos , Epilepsia/genética , Feminino , Fibroblastos/enzimologia , Fibroblastos/patologia , Seguimentos , Granulócitos/patologia , Hexosaminidases/sangue , Humanos , Lactente , Leucócitos/enzimologia , Leucócitos/patologia , Masculino , Monócitos/patologia , Oligossacarídeos/urina , alfa-N-AcetilgalactosaminidaseRESUMO
Se estudió a un niño de 19 meses de edad con un cuadro clínico sugestivo de gangliosidosis GM2: facies peculiar, retardo psicomotor severo, espasticidad generalizada, crisis convulsivas tónicas, macrocefalia, pérdida de la función visual y auditiva, reflejos osteotendinosos exaltados y primer dedo de ambos pies en flexión sostenida; manchas rojo cereza en fondo de ojo y atrofia cerebral demostrada por EEG y TAC. Mediante cromatografía de capa fina se identificaron oligosacáridos en diferentes muestras de orina con un patrón cromatográfico característico. La actividad de las hexosaminidasas A y B en el paciente y sus padre fueron compatibles con homocigocidad y heterocigocidad respectivamente, para la deficiencia de ambas enzimas. Estos resultados permitieron precisar el diagnóstico de gangliosidosis GM2 tipo 2 (Enfermedad de Sandhoff). Se señala la importancia de la identificación de la oligosacariduria
Assuntos
Lactente , Humanos , Masculino , Doença de Sandhoff/diagnóstico , Cromatografia em Camada Fina , Doença de Sandhoff/genética , Eletroencefalografia , Hexosaminidases/deficiência , Oligossacarídeos/urinaRESUMO
Hexosaminidase A activities were determined in tears and peripheral leukocytes of carriers and noncarriers for Tay-Sachs Disease (TSD) as a percentage of total hexosaminidase activity. Correlation between enzyme activities in tears and leukocytes was highly significant (r = 0.75, p less than 0.01). Compared to leukocytes, screening in tears revealed 100% sensitivity, 100% negative predictive value, 86% specificity and 80% positive predictive value. These results indicate that tears are a satisfactory material for mass-screening of TSD-carrier state, but positive results must be confirmed in peripheral leukocytes. Seven heterozygotes were detected among 298 young Ashkenazi Jewish volunteers screened, giving an adjusted frequency of the TSD gene of 0.024.