Galactemia

Goldbloom, Alton; Brickman, Helen F.

doi:10.1016/s0022-3476(46)80064-7

Cited by 45 publications

(8 citation statements)

References 20 publications

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“…In the first half of the twentieth century a number of reports of the disease (sometimes misleadingly called "galactose diabetes") appeared. These established that the disease tends to manifest in early childhood, can be partially reversed by the removal of galactose from the diet and that the liver is one the main organs affected (Mason & Turner , 1935;Bruck & Rapoport , 1945;Mellinkoff et al , 1945;Goldbloom & Brickman , 1946;Greenman & Rathbun , 1948;Bell et al , 1950).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

The molecular basis of galactosemia — Past, present and future

Timson

2016

Gene

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Galactosemia, an inborn error of galactose metabolism, was first described in the 1900s by von Ruess. The subsequent 100 years have seen considerable progress in understanding the underlying genetics and biochemistry of this condition. Initial studies concentrated on increasing the understanding of the clinical manifestations of the disease. However, Leloir's discovery of the pathway of galactose catabolism in the 1940s and 1950s enabled other scientists, notably Kalckar, to link the disease to a specific enzymatic step in the pathway. Kalckar's work established that defects in galactose 1-phosphate uridylyltransferase (GALT) were responsible for the majority of cases of galactosemia. However, over the next three decades it became clear that there were two other forms of galactosemia: type II resulting from deficiencies in galactokinase (GALK1) and type III where the affected enzyme is UDP-galactose 4'-epimerase (GALE). From the 1970s, molecular biology approaches were applied to galactosemia. The chromosomal locations and DNA sequences of the three genes were determined. These studies enabled modern biochemical studies.Structures of the proteins have been determined and biochemical studies have shown that enzymatic impairment often results from misfolding and consequent protein instability. Cellular and model organism studies have demonstrated that reduced GALT or GALE activity results in increased oxidative stress. Thus, after a century of progress, it is possible to conceive of improved therapies including drugs to manipulate the pathway to reduce potentially toxic intermediates, antioxidants to reduce the oxidative stress of cells or use of "pharmacological chaperones" to stabilise the affected proteins.

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Section: Accepted M Manuscriptmentioning

confidence: 99%

The molecular basis of galactosemia — Past, present and future

Timson

2016

Gene

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“…In cases reported by DuShane and Hartman (1951) and by Townsend, Mason, and Strong (1951), a soya bean formula was tried but not tolerated. Goldbloom and Brickman (1946) found such a formula suitable for one baby but not for another. In a number of other cases in which the outcome was satisfactory, nutramigen was used.…”

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confidence: 98%

Galactose Diabetes

Fox¹,

Fyfe²,

Mollison³

1954

BMJ

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“…A unit of enzyme is that amount which will convert one micromole of UDPG to UDPGalactose in an hour. After the incubation period the remaining UDPG is estimated by means of uridine diphosphoglucose dehydrogenase in Goppert (1917) Fanconi (1933) Boer (1932) Mason and Turner (1935) Norman and Fashena (1943) Mellinkoff, Roth and MacLaggan (1945) Bruck and Rapoport (1945) Goldbloom and Brickman (1946) Goldstein and Ennis (1948) Greenman and Rathbun (1948) Bell, Blai., Lindsay and Watson (1950) Donnell and Lann (1951) DuShane and Hartmann (1951) Townsend, Mason and Strong (195 1) Ellenburg and Peterson (1951) Gorter (1951) McCue (1951t De Haas (1951 Enns (1951) Falls, Lowrey and Anderson (1951) Edmonds, Hennigar and Crooks (1952) Langewisch and Bigler (1952) Bray, Isaac and Watkins (1952) Brodie, J. L. (1952) (1958) Pitt (1952) Reiter and Lasky (1952) Johns (1953) Hsia (unpublished data) (1952) Maris and Valcke (1953) Birdsong and Wood (1953) Hartmann, Grunwaldt and James Using these methods the results obtained in this family are given in Table 1. Normal values for this laboratory are given at the top of the Table. The grandfather, who clinically had had a reducing substance in his urine for years (recently proven to be galactose), a large liver and cataracts, was found to have an abnor-mal galactose tolerance test and an enzyme level within the affected range.…”

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confidence: 99%