Article Commentary: The contributions of Louis I Woolf to the treatment, early diagnosis and understanding of phenylketonuria

Fernández, J.R. Alonso; Colón, C.

doi:10.1258/jms.2009.009062

Cited by 11 publications

(12 citation statements)

References 60 publications

(95 reference statements)

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“…In 1951, Louis Woolf demonstrated that the chemical phenotype of PKU responded to the dietary restriction of phenylalanine (Cf. Alonso‐Fernández & Colón, for a review), and was subsequently shown by Dobson, Kushida, Williamson, and Friedman () to improve cognitive function as expressed by increased IQ scores. Subsequently, haploinsufficiency of the gene, PAH , was found to produce PKU (Ledley, Grenett, DiLella, Kwok, & Woo, ), thus establishing a genotype‐phenotype relationship.…”

Section: Introductionmentioning

confidence: 91%

Whither the genotype‐phenotype relationship? An historical and methodological appraisal

Fisch

2017

American J of Med Genetics Pt C

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More than a century ago, Wilhelm Johannsen proposed the terms "genotype" and "phenotype" to study heredity. Much of what we know about genetics and behavior has evolved since then, especially how causality from genotypes can be inferred from observational studies of phenotypes. Unfortunately, there are genotypes that produce complex clinical-behavioral phenotypes-pleiotropy. In addition, there are often many genotypes that produce the same phenotype, adding a layer of complexity in establishing valid genotype-phenotype relationships. Unlike the relative simplicity of some phenotypes, behavioral phenotypes, especially those characteristics considered aberrant, are multidimensional and often not easily defined operationally. An alternate approach which attempts to identify less evident manifestations below the level of the phenotype but along the pathway to the prospective genotype-endophenotypes-could prove useful in detecting genes that generate these markers. However, operational definitions of intermediate phenotypes vary, less overt neurobiological expressions for some disorders-autism-have not been found, and studies of endophenotypes associated with schizophrenia have been not been very successful. Another approach, suggested by Sewall Wright, uses path analysis to identify causal variables that produce phenotypes. Innovative models of causality have been developed recently by genetic epidemiologists that incorporate Mendel's second law, and Mendelian randomization has been successful in identifying genotypes associated with some diseases, for example, diabetes and cancer. Regrettably, shortcomings regarding genetic markers associated with intermediate phenotypes have been found, although there are statistical procedures to remedy matters. As in any science, genetic researchers need to consider carefully the models of causality they choose.

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Section: Introductionmentioning

confidence: 91%

Whither the genotype‐phenotype relationship? An historical and methodological appraisal

Fisch

2017

American J of Med Genetics Pt C

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“…These assays were employed in 1978 in Santiago de Compostela (Galicia) when introducing neonatal screening. For various reasons, Woolf’s original methodology was adapted (see e.g., reference [ 20 , 21 ]). Other assays (e.g., a cystine/homocystine test or Brand’s test) were performed in the same way as Woolf suggested.…”

Section: Woolf’s Interactions With Spanish Investigatorsmentioning

confidence: 99%

“…This paper also tries to acknowledge just that. This paper deals with only part of Dr. Woolf’s work; for further reading see [ 20 , 21 ].…”

Section: Epiloguementioning

confidence: 99%

Dr. Louis Isaac Woolf: At the Forefront of Newborn Screening and the Diet to Treat Phenylketonuria—Biography to Mark His 100th Birthday †

Fernández

2020

IJNS

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“…Poco tiempo después publicó sus hallazgos, denominando imbecillitas phenylpyruvica a la enfermedad de estos niños y postulando que podía estar relacionada con un error en el metabolismo del aminoácido fenilalanina. Así fue la primera vez que se asoció la deficiencia mental con un ECM, el conocido como "oligofrenia fenilpirúvica", "enfermedad de Følling" o, más tarde, PKU (por la presencia en orina de fenilacetona) [24][25][26] . En 1951, el bioquímico inglés Louis I. Woolf sugirió en un artículo que el fallo intelectual de los fenilcetonúricos era debido a una intoxicación por ácido fenilacético y apuntaba a la reducción de fenilalanina en la ingesta como posible tratamiento: "Si la cantidad de fenilalanina y sus productos de degradación pueden reducirse, la función cerebral podrá resultar normal, el que esto lleve a la recuperación o no probablemente dependerá de la duración de la exposición del cerebro a la concentración dañina de la sustancia.…”

Section: Origen De Los Programas De Cribado Neonatalunclassified

Origin of newborn screening programs and their beginnings in Spain

Vicente

Casas²,

Ardanaz³

2017

An Sist Sanit Navar

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resumenLos primeros programas de cribado neonatal de errores congénitos del metabolismo y otras enfermedades endocrinas comenzaron a finales de los años cincuenta y, una década más tarde, se introdujeron en España. Desde entonces han evolucionado mucho, pero de forma muy heterogénea, tanto a nivel internacional como autonómico. Los continuos avances científicos y tecnológicos, fundamentalmente desde el año 2000, han hecho que estas desigualdades se acentúen, haciendo de este tema un inagotable asunto de revisión, debate y discusión hasta nuestros días.Esta revisión pretende recoger, de manera resumida, los orígenes de los programas de cribado neonatal y sus inicios en España, como un primer paso para el aná-lisis de su desarrollo, evolución y situación actual, en unos años en el que se están implementando cambios en muchas comunidades españolas tras la publicación, en noviembre de 2014, de una orden estatal por la cual se regulan y tratan de homogeneizar. AbstrACtThe first newborn screening programs to detect congenital errors of the metabolism and other endocrinal diseases started in the late 1950s and, one decade later, were introduced in Spain. Since then they have evolved considerably, but in a very heterogeneous way, at both the international level and the regional level. The continuous scientific and technological advances, basically since the year 2000, have accentuated these inequalities, making this question into an inexhaustible subject of review, debate and argument up until the present.This review aims to gather, in summarized fashion, the origins of the newborn screening programs and their beginnings in Spain as a first step in analyzing their development, evolution and current situation. This year updating is expected to take place in all the Spanish autonomous regions following publication in November 2014 of a state order that regulates and attempts to homogenize these programs.

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Article Commentary: The contributions of Louis I Woolf to the treatment, early diagnosis and understanding of phenylketonuria

Cited by 11 publications

References 60 publications

Whither the genotype‐phenotype relationship? An historical and methodological appraisal

Whither the genotype‐phenotype relationship? An historical and methodological appraisal

Dr. Louis Isaac Woolf: At the Forefront of Newborn Screening and the Diet to Treat Phenylketonuria—Biography to Mark His 100th Birthday †

Origin of newborn screening programs and their beginnings in Spain

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