Researchers in France have announced the first successful use of preimplantation genetic diagnosis to detect a rare inherited disorder called Ornithine Transcarbamylase (OTCD).
At present, the test can only be used on one family for whom it was devised, but the researchers believe their work may enable them to develop a PGD test for OTCD in other families in the future.
OTCD is a distressing disease linked to the X chromosome, which usually kills boys soon after birth. It occurs in approximately one in 70,000 births. Babies with OTCD have a metabolism which is unable to break down protein effectively. This results in hyperammonemia (an excess of ammonia) which causes death. If detected and treated immediately after birth, a baby may live for longer, but death can occur unexpectedly at any time.
The severity of the symptoms in girls carrying a deficient OTC gene varies widely from nothing to death in the neonatal period. Other symptoms include episodes of extreme irritability, vomiting and lethargy, protein avoidance, ataxia, delayed growth and developmental delay, seizures and comas.
Dr Pierre Ray, from the Hôpital Necker Enfants Malades in Paris, told the European Society for Human Reproduction and Embryology conference in Bologna, Italy, today (Monday 26 June) how one family sought help from geneticists after the mother was found to be an OTCD carrier. Their first child, a boy, had died shortly after birth; a prenatal test on the next pregnancy found the male embryo was also affected and the pregnancy was terminated. Their third baby, a girl, died shortly after birth, at which point the parents felt unable to face another prenatal diagnosis. PGD was their last hope.
PGD involves obtaining embryos by in vitro fertilisation (IVF) and then analysing them for genetic disorders. Only healthy embryos are transferred to the mother's womb.
Dr Ray said: "Diagnosis for OTCD is difficult because of its rarity and because new mutations of the OTC gene are quite frequent. This means that people who are affected by OTCD, or who are carriers, will have different mutations of the gene unless they are from the same family. The diagnostic test we have developed for PGD of OTC can only be used for this particular family as it is unlikely that anyone else will have the same mutation.
"However, to improve the accuracy and reliability of the test, we have been using a marker which is next to the OTC gene, and we believe this marker could be used for other people, although not all OTCD patients. In any case, a tailor-made diagnosis will have to be devised for each couple."
Dr Ray and his colleagues from Necker and the Hôpital Antoine Béclère in Clamart used PCR (polymerase chain reaction) to analyse the OTC gene and find the abnormality which was specific to this particular family. Using standard IVF treatment they collected eggs from the mother, fertilised them using intra cytoplasmic sperm injection (ICSI) and then biopsied the resulting embryos to test for the OTC abnormality.
During the first PGD cycle, out of the six embryos obtained after IVF, three were diagnosed as being unaffected and were transferred back to the mother. No pregnancy resulted. In the second cycle, nine embryos were obtained, there were four affected and five healthy embryos. Again, three healthy embryos were transferred. They are now waiting for pregnancy results after this second attempt.
Note: programme number: O-031
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