User login

Enter your username and password here in order to log in on the website:

Forgot your password?

Please note: While some information will still be current in a year, other information may already be out of date in three months time. If you are in any doubt, please feel free to ask.

Mutations F508del / L227R

My 3 year old son has cystic fibrosis that was diagnosed less than a year ago. The two mutations found were F508del and L227R. As we live in Morocco we do not have a genetic counseling center that can tell us the degree of severity of this type of mutations and how this will develop in the future. Currently he takes pancreatic enzymes and a Pseudomonas was identified in his sputum. I would like to have more information on the degree of severity of his case please.
And actually, pulmonary side so far it has a good follow-up, no more Pseudomonas, a current treatment with colimycin in aerosol. On the other hand he has frequent and fatty stools since his birth. Since we detected his Illness of CF a year ago he takes at each meal the eurobiol in pellets per dosing spoon of 12500 IU. When the meal is fat, I pass to two spoons; Yet I see no improvement. Do I have to go to creon? I have to increase the doses? Thanks so much for your help and happy holidays at all.
The L227R mutation is a “causing CF” mutation when associated with another causing CF mutation as in the case of your child. This mutation has been found only in 7 patients in the CFTR2 database. These 7 patients had an average sweat chloride level of 106 mmol/L comparable to the sweat rate (100 mmol/L) of the nearly 60,000 patients with pancreatic insufficiency listed in this international database.
I have not found any information about the class of the L227R mutation. This mutation is very rare and it is unlikely that studies have been carried out to specify the type of cellular dysfunction caused by this mutation and therefore its class. It is likely in view of the sweat test values of the 6 patients with the same mutations of your child in the international CFTR2 database that the L227R mutation belongs to the class I, II or III mutations responsible, statistically, for a Classical form of cystic fibrosis.

For a patient be cystic fibrosis, he/she must necessarily carry two CF causing mutations one transmitted by the father, one by the mother. A single CF causing mutation is not enough to cause the disease. The parents of a child with cystic fibrosis are necessarily carriers of a CF causing mutation but are not sick. We speak of healthy carriers: they are very numerous, 1 for 33 people about say nearly 2 million people in the population living in France.
Be that as it may, the genetic data have only statistical value. In no case can they predict the evolution of the disease in a given individual because evolution depends on a large number of other environmental factors (pollution, hygiene of life ...) or genetic other than the mutations of the cystic fibrosis gene.

A few tips. It is important that your son:
- take pancreatic enzymes if he has pancreatic insufficiency (it usually manifests as chronic fatty diarrhea, abdominal pain, and insufficient weight and height growth despite appetite sometimes or often increased), diet sufficient calories, fat and salt and that he drink sufficiently to compensate for its losses of water and salt by the sweat, being especially vigilant in case of high heat;
The persistence of fatty and frequent stools of your child despite pancreatic enzyme (one to two spoonfuls of 12,500 IU of eurobiol) suggests that the doses used are insufficient to compensate for his exocrine pancreatic insufficiency. You can increase the doses gradually depending on the condition of the stool. You can easily go up to a total daily dose of 10,000 IU lipase per Kg of body weight.
If, despite increasing the dose to this value, stools do not normalize, it is possible to use a drug to decrease gastric acidity (an inhibitor of the proton pump of the Omeprazole family) and improve the efficiency of pancreatic enzymes.
Increased doses of pancreatic extracts should have had a rapid effect (within 24 to 48 hours) if the increase was sufficient. The daily dose should be spread over all the meals of the day and the enzymes should be taken just before or at the time of the meals. In addition, pancreatic enzymes bottles should be stored away from heat (below 25 ° C) and moisture, ideally in an isothermal container.

- have, in spite of these precautions, the most normal activity possible: that he goes to school, plays and does sports like other children;

- be monitored regularly by a doctor to monitor growth, provide dietary advice, adjust doses of pancreatic enzymes, and treat bronchial infections with active antibiotics against the germ found in the sputum examination. One must be particularly vigilant and reactive if one finds Pseudomonas aeruginosa and control its disappearance after treatment.

Your child seems to have signs of a classic cystic fibrosis. The nature of the mutations, as I indicated above, has a statistical value over a large number of patients but cannot predict for a given individual the severity of the evolution that depends on any other factors.

Hoping to have answered your question. Wishing you also a happy holiday season.
Gilles RAULT, MD, Roscoff CF Center