The Discovery of GALM Deficiency (Type IV Galactosemia) and Newborn Screening System for Galactosemia in Japan

Kikuchi, Atsuo; Wada, Yoichi; Ohura, Toshihiro; Kure, Shigeo

doi:10.3390/ijns7040068

Cited by 9 publications

(18 citation statements)

References 32 publications

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“…The incidence of type I galactosemia ranges from 1:40,000 to 1:60,000. An increased incidence is shown among individuals of Irish origin (1:24,000), whereas the lowest incidence is reported among people of Swedish origin (1:100,000) and Japanese origin (1:788,000) [ 12 , 14 ]. In the United States of America, the prevalence has been reported at values between 1:30,000 and 1:60,000 live births [ 15 , 16 ].…”

Section: Resultsmentioning

confidence: 99%

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The Importance of Neonatal Screening for Galactosemia

2022

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Galactosemia is an inborn metabolic disorder caused by a deficient activity in one of the enzymes involved in the metabolism of galactose. The first description of galactosemia in newborns dates from 1908, ever since complex research has been performed on cell and animal models to gain more insights into the molecular and clinical bases of this challenging disease. In galactosemia, the newborn appears to be born in proper health, having a window of opportunity before developing major morbidities that may even be fatal following ingestion of milk that contains galactose. Galactosemia cannot be cured, but its negative consequences on health can be avoided by establishing precocious diagnosis and treatment. All the foods that contain galactose should be eliminated from the diet when there is a suspicion of galactosemia. The neonatal screening for galactosemia can urge early diagnosis and intervention, preventing complications. All galactosemia types may be detected during the screening of newborns for this disorder. The major target is, however, galactose-1-phosphate uridyltransferase (GALT) deficiency galactosemia, which is diagnosed by applying a combination of total galactose and GALT enzyme analysis as well as, in certain programs, mutation screening. Most critically, infants who exhibit symptoms suggestive of galactosemia should undergo in-depth testing for this condition even when the newborn screening shows normal results. The decision to enroll global screening for galactosemia among the specific population still faces many challenges. In this context, the present narrative review provides an updated overview of the incidence, clinical manifestations, diagnosis, therapy, and prognosis of galactosemia, questioning under the dome of these aspects related to the disease the value of its neonatal monitoring.

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Section: Resultsmentioning

confidence: 99%

“…All galactosemia types may be detected during the screening of newborns for this disorder. However, the major target is GALT deficiency galactosemia, which is diagnosed by assessing blood galactose concentration and erythrocyte GALT enzyme activity and, for certain programs, by performing mutation screening [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Importance of Neonatal Screening for Galactosemia

2022

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“…Recently, type 4 galactosemia was described, which was identified through NBS in Japan [ 25 ]. Variants of the GALM gene ( Table 1 ) were found in a subgroup of newborns.…”

Section: Molecular Genetics Of Galactosemiamentioning

confidence: 99%

“…Five variants have been identified: three nonsense and frameshift variants (p.Arg82*, p.Ile99Leufs*46, and p.Trp311*), leading to premature termination codons and the two missense variants (p.Gly142Arg and p.Arg267Gly). Based on the results of in vitro GALM expression and protein stability assays, all five variant proteins were unstable as compared to wild-type proteins [ 25 , 26 ].…”

Section: Molecular Genetics Of Galactosemiamentioning

confidence: 99%

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Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment

et al. 2022

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Galactosemia is an inborn disorder of carbohydrate metabolism characterized by the inability to metabolize galactose, a sugar contained in milk (the main source of nourishment for infants), and convert it into glucose, the sugar used by the body as the primary source of energy. Galactosemia is an autosomal recessive genetic disease that can be diagnosed at birth, even in the absence of symptoms, with newborn screening by assessing the level of galactose and the GALT enzyme activity, as GALT defect constitutes the most frequent cause of galactosemia. Currently, galactosemia cannot be cured, but only treated by means of a diet with a reduced content of galactose and lactose. Although the diet is able to reverse the neonatal clinical picture, it does not prevent the development of long-term complications. This review provides an overview of galactose metabolism, molecular genetics, newborn screening and therapy of galactosemia. Novel treatments for galactosemia currently being investigated in (pre)clinical studies and potentially able to prevent long-term complications are also presented.

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Addition of galactose‐1‐phosphate measurement enhances newborn screening for classical galactosemia

Daas

Salah

Anikster

et al. 2022

J of Inher Metab Disea

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Galactosemia is an inborn disorder of carbohydrate metabolism of which early detection can prevent severe illness. Although the assay for galactose‐1‐phosphate uridyltransferase (GALT) enzyme activity has been available since the 1960s, many issues prevented it from becoming universal. In order to develop the Israeli newborn screening pilot algorithm for galactosemia, flow injection analysis tandem mass spectrometry measurement of galactose‐1‐phosphate in archived dried blood spots from newborns with classical galactosemia, galactosemia variants, epimerase deficiency, and normal controls, was conducted. Out of 431 330 newborns screened during the pilot study (30 months), two with classical galactosemia and four with epimerase deficiency were identified and confirmed. Five false positives and no false negatives were recorded. Following this pilot study, the Israeli final and routine newborn screening algorithm, as recommended by the Advisory Committee to the National Newborn Screening Program, now consists of galactose‐1‐phosphate measurement integrated into the routine tandem mass spectrometry panel as the first‐tier screening test, and GALT enzyme activity as the second‐tier performed to identify only newborns suspected to be at risk for classical galactosemia. The GALT enzyme activity cut‐off used in the final algorithm was lowered in order to avoid false positives.

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The Discovery of GALM Deficiency (Type IV Galactosemia) and Newborn Screening System for Galactosemia in Japan

Cited by 9 publications

References 32 publications

The Importance of Neonatal Screening for Galactosemia

The Importance of Neonatal Screening for Galactosemia

Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment

Addition of galactose‐1‐phosphate measurement enhances newborn screening for classical galactosemia

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