ABSTRACT
Before the introduction of the NTBC treatment (Orfadine) from two tyrosinemic Hungarian families 1-3 tyrosinemic homozygous male patients died of hepatocellular carcinoma and one patient of hepatocellular carcinoma combined with clear cell renal adenocarcinoma. From the third tyrosinemic family one homozygous girl patient has been treated with NTBC (Orfadine), IMTV-AM, she is symptom-free. Her molecular genetic mutations analysis in the FAH gene detected a common intronel mutation, affecting splicing and of predicted severe effect, IVS6-1 g > t/IVS6-1 g > t with systemic name c.456-1 g > t/c.456-1 g > t (Prof. Magdalena Ugarte).
Subject(s)
Cyclohexanones/therapeutic use , Enzyme Inhibitors/therapeutic use , Hydrolases/genetics , Nitrobenzoates/therapeutic use , Tyrosine/blood , Tyrosinemias/genetics , 4-Hydroxyphenylpyruvate Dioxygenase/antagonists & inhibitors , Carcinoma, Hepatocellular/genetics , Carcinoma, Renal Cell/genetics , Child, Preschool , Fatal Outcome , Homozygote , Humans , Hungary , Kidney Neoplasms/genetics , Liver Neoplasms/genetics , Male , Treatment Outcome , Tyrosinemias/diagnosis , Tyrosinemias/drug therapy , Tyrosinemias/enzymologyABSTRACT
UNLABELLED: AIM was to detect the mutations of alpha-galactosidase A gene in two Hungarian Fabry patients. METHODS: Mutation analysis was performed by polymerase chain reaction (PCR) sequencing of the seven exons and adjacent introns of the alpha-galactosidase A gene. RESULTS: Case 1. (19 y. male patient) Mutation analysis was done for alpha-galactosidase gene, a missence mutation has been identified in the 5th exon, the aspartic acid at codon 266 has been substituted by a tyrosine (notation D266Y) due to a G-T transversion at position 10287 of the alpha GAL-A gene. Case 2. (28 y. male Fabry patient) The GAL-A mutation has been proven to be R220X mutation in exon 5 of the alpha-galactosidase A gene.
