High frequency of type 1 GM1 gangliosidosis in southern Brazil

To the Editor: GM1 gangliosidosis (McKusick 230500) is an inborn error of metabolism (IEM) caused by the deficiency of a specific lysosomal hydrolase, bgalactosidase (EC 3.2.1.23). It is considered to be a very rare disease without ethnic preference (1). GM1 gangliosidosis was the lysosomal storage disease (LSD) most frequently diagnosed in a previous survey conducted at the Regional Laboratory of Inborn Errors of Metabolism (RLIEM) of the Medical Genetics Service of University ‘Hospital de Clı́nicas de Porto Alegre’ (2). In that study, most of the cases corresponded to the infantile type and were originated from Rio Grande do Sul (RS), the southern-most state in Brazil, located along the border with Uruguay and Argentina. In the present study, we collected demographic, clinical and laboratory data from all type 1 GM1 gangliosidosis (GM1-1) patients diagnosed between January 1982 and December 1996 at the RLIEM. Laboratory diagnosis was based on bgalactosidase deficiency in leukocytes and/or a typical chromatographic pattern for urinary oligosaccharides (and no increase in sialic acid) in patients with clinical signs and symptoms compatible with GM1-1. To calculate the incidence of the disease, population data from the National Live Born System of the Health Department of Porto Alegre municipality were used. The calculation of the proportion of heterozygotes in the population was based on the Hardy–Weinberg law. The chisquare test was used to compare the defined characteristics. A total of 13000 high-risk patients were investigated at the RLIEM from 1982 to 1996 and 962 cases of IEM were diagnosed. More than half of these cases (493, 51.3%) presented with LSD. GM1 was the condition most frequently diagnosed (73 cases, 14.8% of the total number of IEM cases). Of these 73 cases, 67 were GM1-1, with a predominance of patients from the state of RS (43 cases, 68.2% of the 63 cases for which the information was available). Parental consanguinity was present in 7 of the 56 cases for which this information was obtained, 4 of them being first cousins and 3 first cousins once removed. This frequency (12.5%), although higher than the usual rate for the region (4%) (3), was half that reported for the remaining cases of GM1-1 described in the literature (25%). The incidence of GM1-1 for the Porto Alegre city was estimated at 1:17000 live births. This rate was obtained by considering that 118609 births occurred in this municipality from 1992 to 1996, 7 of which presented with GM1-1, corresponding to 6 cases per 100000 live births for this period in this region. The proportion of GM1-1 heterozygotes in the population of Porto Alegre was calculated to be 1:67 on the basis of the Hardy–Weinberg law. The incidence of GM1-1 was elevated compared to most figures reported in the literature of 1:100000 (4, 5), 1:200000 (6) and 1:320000 (7). As far as we know, a higher incidence of GM1-1 than that observed in the present study was only reported in Malta (1:3700) (8). A significantly higher proportion of patients with GM1-1 was from RS (43/63, 68.2%) than from other Brazilian states. This could be explained, in part, by the fact that the RLIEM is located in the capital of RS and in a reference hospital. However, of the various other cases of LSD whose biochemical diagnosis was also made at the same laboratory, only 34.8% (139/399) were from RS. This difference between GM1-1 and the other LSD is statistically significant (pB0.001). We believe that a considerable number of individuals bearing mutations for GM1-1 may be concentrated in this state, with a consequent larger number of births of affected infants. A result that supports this idea is the estimate of the proportion of carriers for GM1-1 in the population of Porto Alegre (1:67). This proportion is quite high compared to the information available in the literature with respect to other lysosomal diseases in unselected populations, such as Sanfilippo A, 1:290 (9); Mórquio A, 1:233 (10); Niemann–Pick A, 1:200 (11); and Hurler’s syndrome, 1:100 (12). Another