A 13-year-old girl with the severe form of the Maroteaux-Lamy syndrome (mucopolysaccharidosis Type VI, arylsulfatase B deficiency) has had successful reconstitution with bone marrow from her HLA-MLC-matched sister who had normal arylsulfatase B activity. Full engraftment has been present for 24 months. The following biochemical and clinical changes have occurred: arylsulfatase B activity in peripheral lymphocytes and granulocytes increased to normal levels, and the activity in serial liver-biopsy specimens increased from about 3 per cent of the mean normal level 43 days after transplantation to about 16 per cent at 600 days. Urinary excretion of acid mucopolysaccharide decreased. Ultrastructural evidence of accumulated dermatan sulfate was no longer detectable in bone-marrow cells; in peripheral-blood lymphocytes, granulocytes, or platelets; or in Ito cells of liver. Twenty-four months after engraftment, hepatosplenomegaly was substantially decreased and cardiopulmonary function was normal. Visual acuity and joint mobility were also improved. The patient returned to school and continued to perform well in academic studies. Thus, bone-marrow transplantation provided a source of enzymatically normal cells, which have altered the metabolic and clinical course of the disease.

Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase A, which leads to the pathologic deposition of neutral glycosphingolipids in lysosomes of the vascular endothelium of the heart, brain and kidney. The disease is progressive in hemizygous male patients, with increasing involvement of the major organs leading to death. Because cardiac involvement is a constant feature, echocardiograms were performed on 35 patients with Fabry's disease, 23 hemizygotes (aged 28.6 +/- 14 years) and 12 heterozygotes (aged 31.6 +/- 6 years), to determine whether cardiac involvement could be detected noninvasively. The results demonstrated that hemizygous male patients had a greater aortic root diameter, thicker interventricular septum and greater ventricular mass than did heterozygous female patients. Left ventricular mass per square meter of body surface area correlated well with clinical disease severity (r = 0.68, p less than 0.05), suggesting progressive glycosphingolipid deposition. Older heterozygotes (greater than 25 years old) had more severe evidence of cardiac disease than did younger male patients. Although mitral valve prolapse was identified in 12 (54%) of 23 male hemizygotes and in 7 (58%) of 12 female heterozygotes its presence did not correlate with clinical disease severity or other echocardiographic variables. Therefore, echocardiographic evidence of Fabry's disease appears to correlate with age-related disease severity and may be a useful noninvasive marker to follow disease progression and possible regression when appropriate therapy becomes available.

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Four genetic variants of alcohol dehydrogenase from Drosophila melanogaster have been examined: wild‐type F‐enzyme (from the AdhF strain), the D‐type mutant form (from the AdhD strain), which is catalytically active, and two proteins lacking enzymic activity (from the Adhn11 and Adhn5 strains). The proteins were compared by mapping of tryptic peptides. One pair of difference peptides was seen in the comparisons of the D and F‐type enzymes. These peptides were purified and their sequences determined. The difference between the two proteins was shown to be an exchange at a single position of glycine in the F for glutamic acid in the D‐type protein. This exchange is consistent with the greater acidity of alcohol dehydrogenase from the AdhD strain and can be produced by a single base mutation. The difference between the nll and F‐type proteins was not detected and is suggested to be in a large tryptic peptide. In addition to the difference peptides, other fragments from Drosophila alcohol dehydrogenase were isolated and analyzed. The sequences determined account for approximately 50% of the amino acids in the protein and include regions around the two cysteine residues as well as possible terminal structures. All peptides analyzed were examined for structural identities with horse and yeast alcohol dehydrogenases. No clearly significant similarities were seen between the Drosophila enzyme and the other two proteins but low degrees of homology are possible. From the variations in cysteine‐containing regions large differences appear to exist between the active sites of the insect enzyme and the other alcohol dehydrogenases.

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