Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco

Velázquez, Antonio; Bilbao, Guadalupe; González-Trujillo, José Luis; Hernández, Doris; Pérez-Andrade, Martha Elva; Vela, Marcela; Cicerón, Isabel; Loera-Luna, Antonio; Cederbaum, Stephen D.; Phoenix, Betsy

doi:10.1007/bf00218842

Cited by 9 publications

(9 citation statements)

References 3 publications

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“…The hypothesis that there is a higher PKU prevalence in this area was published several years ago, but has not been confirmed. 30 The clinical data described in Figure 2 are similar to the natural history of the disease reported in the literature, mostly affecting the central nervous system. 1 Contrary to what happens in developed countries, where PKU has grown from a symptomatic disease to a genetic condition modified by early treatment, 31 -33 we still treat patients with the whole phenotypic spectrum.…”

Section: Discussionsupporting

confidence: 70%

Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico

et al. 2011

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Objective To expose causes leading to the delayed arrival of phenylketonuria (PKU) patients at a governmental reference centre (RC), and to describe their clinical characteristics. Material and methods PKU files registered during the past 18 years at the National Institute of Pediatrics in Mexico City were evaluated. Patients were classified into two groups according to their age at arrival: Group I (early reference), patients arriving during the first month of life; and Group II (late reference), those who arrived after thirty days of age. Time and causes of delay were documented. Results Of 57 recorded files, 10 were classified in Group I and 47 in Group II. Causes leading to the late arrival of Group II patients were absence of routine newborn screening (NBS), PKU not included in the routine NBS, sampling after the recommended age, false negative result, results without interpretation and/or instructions to follow, delayed notification of results, poor medical criteria of attending physician, difficulties in obtaining confirmatory tests, and administrative failures. Conclusion The main cause of late referral of PKU patients was the absence of PKU testing. As a developing country, Mexico still faces challenges in the proper functioning and expansion of the NBS programme. Most PKU patients arrived at the RC late, presenting with varying degrees of the clinical spectrum. Incorporating PKU testing into the already established Mexican NBS system and adding quality indicators to guarantee proper operation in all NBS phases is necessary to achieve the goal of identifying, referring, diagnosing, and treating patients promptly.

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Section: Discussionsupporting

confidence: 70%

Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico

et al. 2011

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“…This interpretation is consistent with the settlement history of Mexico, especially by individuals from southern Spain, who colonized El Bajío, particularly the state of Jalisco (‘Los Altos’ region) and its surroundings, during the XVI century . These results support a founder effect and/or genetic drift for c.60+5G>T but not for the Mediterranean c.1066‐11G>A, as was previously suggested .…”

Section: Discussionmentioning

confidence: 99%

“…The mutational spectrum of PAH in Mexico is poorly known; the only study that has been conducted, showed the presence of the c.1066‐11G>A in 5/14 alleles . There is some evidence that PKU in Mexico has a predominance of cases occurring in the Middle West of the country, mainly in the state of Jalisco, where a possible founder effect has been suggested . The PAH genotype, as a predictor of metabolic phenotype, has come to play an important role in assessing the potential responsiveness to treatment with sapropterin dihydrochloride, a synthetic formulation of the active naturally cofactor for PAH, tetrahydrobiopterin (BH 4 ) .…”

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confidence: 99%

Phenylalanine hydroxylase deficiency in Mexico: genotype–phenotype correlations, BH₄ responsiveness and evidence of a founder effect

et al. 2014

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The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is unknown, although it has been suggested that PKU variants could have a differential geographical distribution. Genotype-phenotype correlations and genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4 ) have never been performed. We sequenced the PAH gene and determined the geographic origin of each allele, mini-haplotype associated, genotype-phenotype correlations and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The mutational spectrum included 34 variants with c.60+5G>T being the most frequent (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype-phenotype correlation was concordant in 70.8%. The genotype-based prediction to BH4 -responsiveness was 41.7%, this information could be useful for the rational selection of candidates for BH4 testing and therapy.

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“…Since most of our patients came from the central region of Mexico, the low allelic heterogeneity found might be explained by a Bpopulation of origin^effect-the introduction of few mutant alleles in a region by the immigration of a population which later spread. In the first two centuries of Spanish colonization, most immigrants to the central region of Mexico came from southern Spain (Marqué z-Morfín 1993) and probably introduced few galactosaemic alleles into this region of the country; this effect was described for phenylketonuria in Mexico (Velá zquez et al 1996), but further studies are required to confirm this hypothesis.…”

Section: Resultsmentioning

confidence: 76%

Low allelic heterogeneity in a sample of Mexican patients with classical galactosaemia

Velázquez-Aragón

Alcántara-Ortigoza

Vela-Amieva

et al. 2008

J of Inher Metab Disea

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Classical galactosaemia is an autosomal recessive disease of galactose metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). Galactosaemia is not included in the neonatal screening programme in Mexico and it is necessary to implement methodologies for prompt diagnosis of these patients to establish treatment. To date, more than 190 mutations in the GALT gene have been reported, most in caucasian populations, but there have been no reports of mutations in Latin-American populations. We report here the mutational spectrum in 19 Mexican galactosaemic patients. The most frequent mutations were p.Q188R, p.N314D and IVS2-2A>G, which together represented 71% of detected mutations. The mutation IVS2-2A>G, which has been detected only in Hispanics, was thought to generate a null allele; we identified one patient with a homozygous IVS2-2A>G mutation who showed a mild deficiency of enzyme value in erythrocytes. One patient homozygous for Duarte 2 (p.N314D, IVS5+62G>A) is probably due to a partial uniparental disomy of chromosome 9. In addition, a novel mutation c.336T>C (p.S112R) was detected in one patient with severe enzymatic deficiency. Despite the small number of patients studied, our results suggest that classical galactosaemia shows low allelic heterogeneity in Mexican patients, in contrast what is observed in other Mendelian disorders such as cystinosis or autosomal dominant hypercholesterolaemia. This low allelic heterogeneity might be explained by a "population of origin" effect in the central region of Mexico, as has been described for phenylketonuria.

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Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco

Cited by 9 publications

References 3 publications

Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico

Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico

Phenylalanine hydroxylase deficiency in Mexico: genotype–phenotype correlations, BH₄ responsiveness and evidence of a founder effect

Low allelic heterogeneity in a sample of Mexican patients with classical galactosaemia

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Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco

Cited by 9 publications

References 3 publications

Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico

Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico

Phenylalanine hydroxylase deficiency in Mexico: genotype–phenotype correlations, BH4 responsiveness and evidence of a founder effect

Low allelic heterogeneity in a sample of Mexican patients with classical galactosaemia

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Phenylalanine hydroxylase deficiency in Mexico: genotype–phenotype correlations, BH₄ responsiveness and evidence of a founder effect