Correlation of cognitive, neurologic, and ovarian outcome with the Q188R mutation of the galactose-1-phosphate uridyltransferase gene

Kaufman, Francine; Reichardt, Juergen K.V.; Ng, W.; Xu, Yan-Kang; Manis, Franklin R.; McBride‐Chang, Catherine; Wolff, Jon A.

doi:10.1016/s0022-3476(94)70197-0

Cited by 56 publications

(30 citation statements)

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“…Determining total body oxidation of 13 C-D-galactose to 13 CO 2 (breath test). After a baseline breath collection, patients and control volunteers were administered an oral bolus of 7 mg of 1-C 13 -D-galactose per kilogram of body weight and breath was collected at 90, 100, 110, and 120 min.…”

Section: Methodsmentioning

confidence: 99%

“…After a baseline breath collection, patients and control volunteers were administered an oral bolus of 7 mg of 1-C 13 -D-galactose per kilogram of body weight and breath was collected at 90, 100, 110, and 120 min. 13 C enrichment of CO 2 was measured in collected breath samples by automated, gas-isotope ratio, mass spectrometry as previously described (16,17,21). Micromoles of expired 13 CO 2 per minute were determined from the estimated CO 2 production rate obtained from calculations using the Weir equation (22) based on a fasting respiratory quotient (RQ) of 0.80.…”

Section: Methodsmentioning

confidence: 99%

“…Because hGALT activity in peripheral erythrocytes may not indicate hGALT activity in other organs, we developed an oral 2-h breath test that measures the percentage of labeled 13 C-Dgalactose to 13 CO 2 in expired air (16). We stratified patients with "classic" galactosemia into two categories of impaired total body galactose oxidation, Ͻ5% and Ն5% cumulative percentage dose (CUMPCD) recovered at 120 min.…”

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confidence: 99%

“…In this prospective study, we validated a simplified test of total body 13 C-D-galactose oxidation from an oral bolus to 13 CO 2 in expired air (the "breath test") against mutant hGALT alleles of known severity. We then compared this breath test against four other biochemical parameters as potential risk indicators for verbal dyspraxia.…”

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Verbal Dyspraxia and Galactosemia

et al. 2003

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Classical galactosemia is an autosomal recessive disorder resulting from deficient galactose-1-phosphateuridyl transferase (GALT) activity. Verbal dyspraxia is an unusual outcome in galactosemia. Here we validated a simplified breath test of total body galactose oxidation against genotype and evaluated five potential biochemical risk indicators for verbal dyspraxia in galactosemia: cumulative percentage dose (CUMPCD) of 13 CO 2 in breath, mean erythrocyte galactose-1-phosphate, highest erythrocyte galactose-1-phosphate, mean urinary galactitol, and erythrocyte GALT activity. Thirteen controls and 42 patients with galactosemia took a 13 C-galactose bolus, and the (CUMPCD) of 13 CO 2 in expired air was determined. Patients with Ͻ5% CUMPCD had mutant alleles that severely impaired human GALT enzyme catalysis. Patients with Ն5% CUMPCD had milder mutant human GALT alleles. Twenty-four patients consented to formal speech evaluation; 15 (63%) had verbal dyspraxia. Dyspraxic patients had significantly lower CUMPCD values (2.84 Ϯ 5.76% versus 11.51 Ϯ 7.67%; p Ͻ 0.008) and significantly higher mean erythrocyte galactose-1-phosphate (3.38 Ϯ 0.922 mg/dL versus 1.92 Ϯ 1.28 mg/dL; p ϭ 0.019) and mean urinary galactitol concentrations (192.4 Ϯ 75.8 mmol/mol creatinine versus 122.0 Ϯ 56.4; p ϭ 0.048) than patients with normal speech. CUMPCD values Ͻ5%, mean erythrocyte galactose-1-phosphate levels Ͼ2.7 mg/dL, and mean urinary galactitol levels Ͼ135 mmol/mol creatinine were associated with dyspraxic outcome with odds ratios of 21, 13, and 5, respectively. We conclude that total body oxidation of galactose to CO 2 in expired air reflects genotype and that this breath test is a sensitive predictor of verbal dyspraxia in patients with galactosemia. Classical galactosemia is an autosomal recessive disorder resulting from deficient human galactose-1-phosphate uridyl transferase (hGALT) (1, 2). Currently, Ͼ180 mutations produce Ͻ1% of hGALT activity when present as homozygous or compound heterozygous mutant genotypes (3-5). Newborns with galactosemia exhibit elevated concentrations of erythrocyte galactose-1-phosphate and excess galactitol in the urine. If newborn screening, retrieval, diagnosis, and removal of galactose from the diet occur before 5-7 d of life, then the neonatal signs of hepatotoxicity, jaundice, anorexia, and diarrhea are prevented or resolve (6, 7). However, infants who have classical galactosemia and are treated continue to have elevated erythrocyte galactose-1-phosphate and urinary galactitol concentrations after initiation of a galactose-restricted diet. These compounds remain elevated throughout the life of the patient; are indicators of the environment (compliance), genotype, epigenetic phenomenon (8 -10); and are implicated in the enigmatic outcomes in galactosemia (7, 8, 10 -13).Roughly half of the children with classical galactosemia manifest verbal dyspraxia (7,10,14). This expressive speech problem results from an impaired ability to program the muscles needed for speech. Children exhibit "chaotic" speech...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Verbal Dyspraxia and Galactosemia

et al. 2003

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“…7 Bununla beraber diğer çalışmalarda, kognitif fonksiyonlarda kayıp, nörolojik bulgular ve ovaryan yetmezlik yö-nünden genotiple fenotip arasında korelasyon saptanmamıştır. 8,9 Bundan dolayı klasik galaktozemili bireylerde mutasyon analizi, tedavi ve prognoz için yol gösterici değildir. Birinci olguda, klasik galaktozemide sık karşılaşılan klinik bulgulardan farklı olarak, daha nadir görülen masif asit ve psödotü-mör serebri düşündüren bulgular vardı.…”

Section: Discussionunclassified