Summary: Over the last 15 years, we have performed a total of 30 haematopoietic stem cell transplants on 27 children suffering from Hurler's syndrome. These children were of median age 11 months at the time of diagnosis and 25 months at the time of transplantation. The phenotype was severe in 21 cases (78%). The donor was familial in 13 cases: nine genotypically identical, one phenotypically identical father and three HLA-mismatched donors. Unrelated donors were selected in 17 cases: four phenotypically identical and 13 with 1–4 HLA mismatches. The conditioning regimen generally consisted of busulphan 600 mg/m 2 plus cyclophosphamide (Endoxan ® ) 260 mg/kg and cyclosporin with methotrexate for GvHD prophylaxis. Rabbit anti-thymocyte globulin (Thymoglobuline ® ) was given for all unrelated or familial mismatched transplantations. The median nucleated cell dose infused was 6.00 × 10 8 TNC/kg. No bone marrow (apart from one) was T cell depleted. For first transplants, engraftment was observed in 23/27 patients (pts) (85%). Primary graft failure was observed in 4/27 patients (16%), two were retransplanted from an unrelated donor, one with success. Four patients have died. The primary cause of death was infection in three cases (TRM : 11%) and disease progression in one case, after primary graft failure. Of the 23 living patients, two have disease progression after graft failure and 21 (78%) have functional grafts with a favourable long-term outcome after a median follow-up of 4.7 years, having either full or mixed chimaerism. Among surviving patients with functional grafts, 13 (62%) were transplanted from unrelated donors of whom 10 (77 %) had HLA disparities. There was a remarkably low incidence of GvHD. In our experience, haematopoietic stem cell transplantation using an HLA-matched familial donor or an HLA-matched or -mismatched unrelated donor without T cell depletion or irradiation can achieve a favourable outcome in Hurler's syndrome, with improved cognitive function, but with a limited effect on the corneas and skeleton.

Conclusion Our patient was not an ideal candidate since she was not clinically completely asymptomatic and presented with abnormal MRI and decreased nerve conduction when the metachromatic leukodystrophy was diagnosed in her older sibling. Nevertheless, 2 years after graft the deterioration did not progress and the MRI improved, while her brother became bed‐ridden within few months after the same initial symptoms. These favourable results need further confirmation after several years since significant differences in course have been observed in siblings (Clarke et al 1989).

Neonatal screening of Duchenne Muscular Dystrophy using serum CK level measurement has been performed for 10 years in a part of the Rhône-Alpes area (40,000 newborns per year). This test avoids consecutive cases in an affected family by mean of an early genetic counselling. So, 10 potential DMD boys have been avoided (i.e. one out of five of the D.M.D., as a whole which would be born during this same ten year study). Details on familial structures and efficiency of genetic counselling are given, and this efficiency will be increased by the DNA study of the concerned families.

Systematic neonatal screening programme for DMD has been set up since June 1975. Constant and specific SCK increase in DMD newborn can be found on whole dried blood between the 5th and 8th day after birth. The amount of false positives is small : 1,6%. At the first control, DMD diagnosis is very probable and is made certain by EMG and muscle microscopic observations. For a period of 3 years and 6 months, we have achieved 138 579 screening tests, and 12 DMD were found, among 71 091 boys (1/5 929 male births). Genealogical data from 11 families out of the 12 lead to identify 93 women relatives as possible carriers; 23 of them are menstruating women who benefit by recognition and receive genetic information several years before the DMD clinical diagnosis in the first family's proband could have been done. Systematic neonatal screening programme for DMD seems to be a means to reduce the incidence of DMD to the theoretical mutation cases.

Dosage de la creatine kinase serique. Sur 109, 100 nouveau-nes testes entre 1975 et 1978, 9 cas diagnostiques

Systematic screening for congenital hypothyroidism was started in Lyon in september 1976. This screening was coupled with PKU, using the same dried blood samples on filter paper obtained on the 5th day of life. TSH levels were determined by radioimmunoassay adapted for dried blood samples (Kit Abbott). In 24 months, 56 176 samples were analyzed. The critical level calling for control was successively raised from from 20 to 30, now 40 microUI/ml of serum. A high level of TSH was found in 307 children (0,55%). Pathological deliveries were found in most of these infants (neonatal injury, cesarean, section forceps or ocytocic perfusion, neonatal icterus) and a second or a third measurement showed normal TSH level. Congenital hypothyroidism, was found detected in 18 infants: 12 ectopic gland, 5 athyreosis and 1 dyshormonogenesis. Treatment was begun at a mean age of 38 days (29 to 50 days).