Galactosemia Diagnosis Gets an Upgrade

Bennett, Michael J.

doi:10.1373/clinchem.2010.145359

Cited by 12 publications

(10 citation statements)

References 7 publications

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“…Increased galactose-1-phosphate accumulates in the liver, kidney, brain, tongue, lens, and cutaneous fibroblasts, and causes injury. In many patients, jaundice, hepatosplenomegaly, hepatic failure, feeding difficulties, hypoglycemia, renal tubular dysfunction, muscular hypotonia, sepsis, and cataracts are observed following intake of galactose in the neonatal period (3,4). Rapid symptom regression occurs with early initiation of treatment, but outcomes that affect life negatively in the short and long term may be observed (1).…”

Section: Introductionmentioning

confidence: 99%

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Clinical, molecular, and genetic evaluation of galactosemia in Turkish children

et al. 2016

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Aim: Galactosemia is a carbohydrate metabolism disorder with autosomal recessive inheritance. The most frequent enzyme deficiency is galactose-1-phosphate-uridylytransferase, which causes classic galactosemia. When the enzyme is absent, an infant cannot metabolize galactose-1-phosphate and it cumulates in liver, kidney, brain, tongue, lens, and skin. This study aimed to evaluate the clinical and molecular characteristics of patients with galactosemia, which is observed more frequently in our country than anywhere else in the world. Material and Methods:This is a retrospective study that includes the moleculer and genetic charcteristics of 14 patient who were diagnosed as having galactosemia between January 2009 and January 2011.Results: Nine patients were male and 5 female. Consanguineous marriage was detected in the family history of 7 patients. One patient had a history of a deceased sibling with a confirmed diagnosis of galactosemia. The main reasons for admission to the hospital were jaundice in 9, hypoglycemia in 2, sepsis in 2, and elevated liver enzymes in 1 patient. The Beutler test was positive in all patients. The mean enzyme activity was 0.36±0.26 µmol/mL. Only 6 of our cases were diagnosed in the early period (first 15 days). Cataract was present in four patients. Q188R mutation was observed in 13 patients, and homozygote N314D and homozygote E340X mutations were observed in one patient. Three patients had impaired neurologic development according to the Denver Developmental Screening Test II. Conclusion:The most common genetic abnormality was Q188R mutation. Only 43% of our patients's disease could be diagnosed at an early stage. We suggest that galactosemia should be included in the national newborn screening program in order to make earlier diagnoses. (Turk Pediatri Ars 2016; 51: 204-9)

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Section: Introductionmentioning

confidence: 99%

“…Close monitoring is necessary in patients with classic galactosemia because of all these factors mentioned above (3)(4)(5). These patients will remain on a special diet throughout their lives and it is recommended that they are followed up by a multidisciplinary team.…”

Section: Introductionmentioning

confidence: 99%

Clinical, molecular, and genetic evaluation of galactosemia in Turkish children

et al. 2016

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“…In humans, a deficiency of the second enzyme of the Leloir pathway, galactose-1-phosphate uridylyltransferase (GALT, E.C. 2.7.7.12), results in the autosomal recessive, potentially lethal disorder classic galactosemia ( OMIM 230400) (Fridovich-Keil and Walter, 2008; Bennett, 2010; Bosch, 2011). …”

Section: Introductionmentioning

confidence: 99%

Oxidative stress contributes to outcome severity in a Drosophila melanogaster model of classic galactosemia

Jumbo-Lucioni

Hopson

Hang

et al. 2012

Disease Models &Amp; Mechanisms

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SUMMARYClassic galactosemia is a genetic disorder that results from profound loss of galactose-1P-uridylyltransferase (GALT). Affected infants experience a rapid escalation of potentially lethal acute symptoms following exposure to milk. Dietary restriction of galactose prevents or resolves the acute sequelae; however, many patients experience profound long-term complications. Despite decades of research, the mechanisms that underlie pathophysiology in classic galactosemia remain unclear. Recently, we developed a Drosophila melanogaster model of classic galactosemia and demonstrated that, like patients, GALT-null Drosophila succumb in development if exposed to galactose but live if maintained on a galactose-restricted diet. Prior models of experimental galactosemia have implicated a possible association between galactose exposure and oxidative stress. Here we describe application of our fly genetic model of galactosemia to the question of whether oxidative stress contributes to the acute galactose sensitivity of GALT-null animals. Our first approach tested the impact of pro- and antioxidant food supplements on the survival of GALT-null and control larvae. We observed a clear pattern: the oxidants paraquat and DMSO each had a negative impact on the survival of mutant but not control animals exposed to galactose, and the antioxidants vitamin C and α-mangostin each had the opposite effect. Biochemical markers also confirmed that galactose and paraquat synergistically increased oxidative stress on all cohorts tested but, interestingly, the mutant animals showed a decreased response relative to controls. Finally, we tested the expression levels of two transcripts responsive to oxidative stress, GSTD6 and GSTE7, in mutant and control larvae exposed to galactose and found that both genes were induced, one by more than 40-fold. Combined, these results implicate oxidative stress and response as contributing factors in the acute galactose sensitivity of GALT-null Drosophila and, by extension, suggest that reactive oxygen species might also contribute to the acute pathophysiology in classic galactosemia.

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“…Galaktoz ve metabolitlerinin ayrıca tiroid fonksiyonlarını da etkileyebileceği bildirilmiştir. 20 Bunun nedeninin karaciğer kaynaklı olan tiroid bağlayıcı globulinin yetersiz sentezi olduğu düşü-nülmektedir. Geçici hipotiroksinemi preterm bebeklerde sık görülmesine rağmen term bebeklerde nadirdir.…”

Section: Discussionunclassified