Molecular basis and clinical presentation of classic galactosemia in a Croatian population

Ramadža, Danijela Petković; Sarnavka, Vladimir; Vuković, Jurica; Fumić, Ksenija; Krželj, Vjekoslav; Lozić, Bernarda; Pušeljić, Silvija; Pereira, H. Ferrer; Silva, Maria João; Almeida, Isabel Tavares de; Barić, Ivo; Rivera, Isabel

doi:10.1515/jpem-2017-0302

Cited by 5 publications

(7 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fifteen are not found in HGMD or ARUP GALT database and one has previously been published in 1993 . Only a few variants are frequent, which agrees with reports from other countries . The most common variant, among Swedish patients with classical galactosemia is p.(Gln188Arg) with an allele frequency of 51%.…”

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

Heterogeneity of disease‐causing variants in the Swedish galactosemia population: Identification of 16 novel GALT variants

Ohlsson

Hunt²,

Wedell

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

The aim was to determine disease‐causing variants in the GALT gene which codes for the enzyme galactose‐1‐phosphate uridylyltransferase. Loss of activity of this enzyme causes classical galactosemia—a life threatening, treatable disorder, included in the Swedish newborn screening program since 1967. A total of 66 patients with the disease are known in Sweden and 56 index patients were investigated. An additional two patients with Duarte galactosemia were included. The disease‐causing variants were identified in all patients. As reported from other countries only a few variants frequently recur in severe disease. The two variants p.(Gln188Arg) (c.563A>G) and p.(Met142Lys) (c.425T>A) are present in several index patients whereas the remaining are found in one to three patients each. The most common variant, p.(Gln188Arg), has an allele frequency of 51% in the cohort. A total of 16 novel variants were found among the 33 different variants in the cohort. Two of these are synonymous variants affecting splicing, demonstrating the importance of the evaluation of synonymous variants at the cDNA level. Concise sentence: Galactosemia is a rare disease in Sweden and the disease‐causing variants are heterogenous including two synonymous variants.

show abstract

Section: Discussionsupporting

confidence: 82%

“…20 Only a few variants are frequent, which agrees with reports from other countries. 30,31,37,38 The most common variant, among Swedish patients with classical galactosemia is p.(Gln188Arg) with an allele frequency of 51%.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of disease‐causing variants in the Swedish galactosemia population: Identification of 16 novel GALT variants

Ohlsson

Hunt²,

Wedell

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Dio rezul- tata analize gena GALT u naših bolesnika već su opi sali Petković Ramadža i suradnici. 35 Aktivnost enzima GALT mjerena je u 62,5% (15/24) ispitanika, od čega je u 60% (9/15) bila nemjerljiva. Za dva ispitanika s nemjerljivom aktivnošću enzima genotip nije bio poznat.…”

Section: Rezultatiunclassified

“…Rezultati genske analize većine naših ispitanika u članku Petković Ramadže i suradnika pokazuju da je spektar mutacija klasične galaktozemije u Hrvatskoj ograničen na četiri mutacije, što bi se moglo iskoristiti za smišljanje prikladne strategije brze molekularne dijagnostike u novorođenčadi, osobito ako se uvede novorođenački probir na galaktozemiju. 35 Sve mutacije u naših ispitanika otprije su opisane i povezane s teškom kliničkom slikom. Dvije najčešće mutacije, c.563A>G i c.855G>T, udružene su s potpunim gubitkom aktivnosti enzima GALT.…”

Section: Raspravaunclassified

“…Dio rezultata analize gena GALT u naših bolesnika već su opisali Petković Ramadža i suradnici. / Results of GALT gene analysis have partly been already published by Petković Ramadža et al35 ; b Broj ispitanika za koje su podatci bili poznati / number of patients for whom the data were known; U zdravoj populaciji / in healthy population: c > 0,3 µkat/gHb, d > 4, e 2,3 -25 U/gHb, N -nemjerljivo / immeasurable…”

unclassified

See 1 more Smart Citation

Experiences with galactosemia in Croatia

2023

View full text Add to dashboard Cite

SAŽETAK. Cilj našeg rada bio je opis osobitosti bolesnika s klasičnom galaktozemijom iz Hrvatske uz prikaz bolesnika s manjkom galaktokinaze i bolesnika koji je dvostruki heterozigot za mutacije gena galaktoza-1-fosfat--uridiltransferaze (GALT) i galaktoza-4'-epimeraze (GALE). Istraživanje je obuhvatilo 24 bolesnika s dijagnozom klasične galaktozemije postavljenom u razdoblju od 1977. do 2020. godine. Dijagnoza je postavljana na temelju kliničke slike, koncentracije galaktoze u krvi i urinu, a potvrđivana mjerenjem aktivnost galaktoza-1-fosfat--uridil-transferaze i/ili analizom gena GALT. Simptome u novorođenačkom razdoblju razvilo je 87% bolesnika, a jedan bolesnik je umro. Medijan dobi pri pojavi prvih simptoma bio je četiri dana, a pri početku dijete jedanaest i pol dana. Barem jednu dugoročnu komplikaciju razvilo je 78,3% bolesnika. Među njima su bili poremećaji psihomotoričkog razvoja (68,2%), ponašanja (31,8%) i govora (55,6%), smanjene intelektualne sposobnosti (46,2%), druge neurološke komplikacije (40,9%), katarakta (18,2%) i smanjena mineralna gustoća kostiju (27,8%). Zatajenje jajnika razvilo je 66,7% bolesnica starijih od 10 godina. Uspoređujući bolesnike iz iste obitelji, iako je početak liječenja u drugorođenih bio raniji, čini se da dugoročne komplikacije nisu bile povezane s redoslijedom rođenja. Ova studija pokazuje da većina bolesnika s klasičnom galaktozemijom razvije simptome u novorođenačkom razdoblju i, unatoč strogom pridržavanju dijete, dugoročne komplikacije. Mnogi su još nepoznati čimbenici koji utječu na patogenezu i klinički tijek bolesti, zbog čega su potrebna daljnja istraživanja klasične galaktozemije.

show abstract

Neonatal classic galactosemia—diagnosis, clinical profile and molecular characteristics in unscreened Turkish population

Çelik

Akdeniz

Özbek

et al. 2022

Journal of Tropical Pediatrics

View full text Add to dashboard Cite

Background Classic galactosemia (CG) is a rare hereditary disease that can cause serious morbidity and death if it is not diagnosed and treated in early periods of life. Clinical findings usually occur in the neonatal period after the neonate is fed with milk that contains galactose. Most patients are presented with jaundice, hepatomegaly, hypoglycemia and cataracts. Objective We aimed to document the clinical, molecular characteristics, regional estimated incidence and time of diagnosis in newborn with CG. Materials and method The data of 63 newborn with CG who were diagnosed and followed up between January 2011 and January 2018 were analyzed retrospectively. Results During the study period, 63 (33 boys and 30 girls) newborns were diagnosed with CG. The median gestational age was 39 weeks (33–42). Major presenting symptoms were jaundice 90.5% and cataract 41.2%. The mean age at first symptom was 12 ± 7.4 days while the mean age at diagnosis was 18.9 ± 10.6 days. Nearly half of the patients (55.5%) were diagnosed later than the postnatal 15th day. Genetic analysis was performed on 56 patients and homozygous Q188R mutation was found in 92.8%. There were signs of sepsis in 33.3% of the cases. Six patients died due to sepsis. There was consanguinity in 84.1% of the parents and regional estimated incidence was calculated as 1 in 6103 live births. Conclusion Q188R mutation was found in 92.8% of our cases. The regional estimated incidence was found as 1 in 6103 live births. Our study strongly supports that galactosemia should be included in the national newborn screening program.

show abstract

Molecular basis and clinical presentation of classic galactosemia in a Croatian population

Abstract: This is the first report on mutational and phenotypic spectra of classic galactosemia in Croatia that expands the knowledge on the mutational map of the GALT gene across Europe and reveals the genetic homogeneity of the Croatian population.

Cited by 5 publications

References 12 publications

Heterogeneity of disease‐causing variants in the Swedish galactosemia population: Identification of 16 novel GALT variants

Heterogeneity of disease‐causing variants in the Swedish galactosemia population: Identification of 16 novel GALT variants

Experiences with galactosemia in Croatia

Neonatal classic galactosemia—diagnosis, clinical profile and molecular characteristics in unscreened Turkish population

Contact Info

Product

Resources

About