Expansion of the clinical phenotype of <scp>GALE</scp> deficiency

Markovitz, Rebecca; Owen, Nichole; Satter, Lisa Forbes; Kirk, Susan E.; Mahoney, Donald H.; Bertuch, Alison A.; Scaglia, Fernando

doi:10.1002/ajmg.a.62384

Cited by 9 publications

(10 citation statements)

References 12 publications

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“…Previous studies have shown that proper glycosylation is crucial to normal hemopoiesis, in particular to megakaryocyte and platelet development; defects in genes regulating sugar metabolism and glycosylation can be associated with bone marrow failure [7,8]. Moreover, in an animal model of galactosemia, newborn GALT gene-trapped mice presented manifestations of oxidative stress in red blood cells (altered glutathione/oxidized glutathione ratio), a fact to which our patient's anemia could be also attributed [2].…”

Section: Discussionmentioning

confidence: 66%

“…This is a case of galactosemia in a neonate who presented with both acute liver failure and cytopenias. Neonatal acute liver failure has been well described in the literature in patients with galactosemia; on the contrary, cytopenias have only rarely been reported either in the context of secondary hemophagocytic lymphohistiocytosis in galactosemia [3], similar to other metabolic disorders [5,6] or terms of inherited/chronic thrombocytopenia or pancytopenia associated with mutation of UDP-galactose-4epimerase [7,8]. Hemophagocytic lymphohistiocytosis was not confirmed in our patient because only three out of the eight diagnostic criteria [4] were fulfilled (cytopenia, low fibrinogen, and elevated ferritin).…”

Section: Discussionmentioning

confidence: 99%

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Transient Cytopenias as a Rare Presentation of Classic Galactosemia

Gianniki¹,

Nikaina²,

Avgerinou³

et al. 2022

Cureus

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Although galactosemia can be detected through neonatal screening, some cases are characterized by rapid and severe presentation before screening results become available. We report the case of a neonate with classic galactosemia presenting with acute liver failure and cytopenias (thrombocytopenia, anemia, and neutropenia). Neonatal screening results showed increased galactose and phenylalanine levels. The diagnosis of galactosemia was confirmed by the measurement of galactose-1-phosphate uridyltransferase (GALT) activity in erythrocytes. Two mutations of the GALT gene (c.563 A>G [p. Q188R] and c.957C>A [p.H319Q]) were revealed. High clinical suspicion of galactosemia is crucial to identify, as early as possible, cases with classical or even unusual presentation, and to initiate early treatment that could change the disease course and improve outcomes. Cytopenias should be included in the broad phenotypic spectrum of galactosemia.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Transient Cytopenias as a Rare Presentation of Classic Galactosemia

Gianniki¹,

Nikaina²,

Avgerinou³

et al. 2022

Cureus

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“…Galactosemia includes a rare group of hereditary disorders of galactose metabolism. To date, four types have been described, each affecting a different step in the main route of galactose disposal: type I, resulting from GALT deficiency; type II, resulting from GALK1 deficiency; type III, resulting from GALE deficiency; and the recently described type IV galactosemia, resulting from GALM deficiency [ 20 , 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…Partial transferase deficiency is more common than classic galactosemia, is asymptomatic, and is diagnosed by screening the newborn based on a determination of moderately increased blood galactose and/or low transferase activity. The condition should be taken into consideration for the newborn who is underweight or has any of the above signs and symptoms [ 17 , 21 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

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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“…Most GALE deficiencies consist of the “peripheral” type, in which the deficiency is restricted to red and white cells, and has virtually no symptoms. GALE deficiency, however, is considered a continuum disorder rather than a binary condition [ 19 ] and it has also been associated with thrombocytopenia [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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

Kikuchi

Wada

Ohura

et al. 2021

IJNS

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The Leloir pathway, which consists of highly conserved enzymes, metabolizes galactose. Deficits in three enzymes in this pathway, namely galactose-1-phosphate uridylyltransferase (GALT), galactokinase (GALK1), and UDP-galactose-4′-epimerase (GALE), are associated with genetic galactosemia. We recently identified patients with galactosemia and biallelic variants in GALM, encoding galactose epimerase (GALM), an enzyme that is directly upstream of GALK1. GALM deficiency was subsequently designated as type IV galactosemia. Currently, all the published patients with biallelic GALM variants were found through newborn screening in Japan. Here, we review GALM deficiency and describe how we discovered this relatively mild but not rare disease through the newborn screening system in Japan.

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Expansion of the clinical phenotype of GALE deficiency

Cited by 9 publications

References 12 publications

Transient Cytopenias as a Rare Presentation of Classic Galactosemia

Transient Cytopenias as a Rare Presentation of Classic Galactosemia

The Importance of Neonatal Screening for Galactosemia

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

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