The clinical course in Type A Niemann-Pick disease is similar among affected patients and is characterized by a relentless neurodegenerative course that leads to death, usually within 3 years.
Fabry disease is an X-linked inborn error of metabolism resulting from deficient activity of alpha-galactosidase A. Although several case reports have suggested an association between Fabry disease and airway obstruction, this has not been investigated in a large series of patients. We studied 25 unselected, consecutive, enzymatically diagnosed men referred to a General Clinical Research Center for evaluation. Thirty-six percent complained of dyspnea, and 24% had cough and/or wheezing. Symptoms were similar in smokers and nonsmokers. Nine (36%) had airway obstruction on spirometry; this finding was associated with age > or = 26 yr (p < 0.05) and dyspnea or wheezing (p < 0.005), but only weakly with smoking (p = 0.062). Five of eight patients responded to bronchodilators, but all 10 methacholine challenges were negative. Chest radiographs revealed normal lung fields in 24 patients and streaky bibasilar densities in one. No pulmonary uptake occurred on 67Ga citrate scans (18 patients) and 111In-tagged leukocyte scans (16 patients). Specific alpha-galactosidase A mutations were identified in 17 patients; all three patients with frameshift mutations and both subjects with the D264V missense mutation had obstructive impairment. We conclude that airway obstruction commonly occurs in patients with Fabry disease regardless of smoking history, and it increases with age. The presence of obstruction may be associated with certain mutations and most likely results from fixed narrowing of the airways by accumulated glycosphingolipid.
Pulmonary disease is a well-known complication of Type 1 Gaucher disease (GD), although its incidence is not well established and its severity varies. The purpose of this study was to determine the frequency and extent of pulmonary involvement in patients with GD. Pulmonary involvement was assessed by history, physical examination and chest radiograph in 150 consecutive patients with Type 1 GD presenting at a specialized center for genetic diseases. Five patients were noted to have clinical evidence of pulmonary involvement. Full pulmonary function tests were performed in these five patients and in an additional 13 patients randomly selected from the remaining 145. Many of the 18 patients also underwent radionuclide body imaging with 67 Gallium citrate and 111Indium-tagged leucocyte scans, as well as incremental cardiorespiratory exercise tests. Lung biopsies were available in two patients with lung disease, and a second examination of lung tissue was performed in one of these two patients post-mortem. Clinical lung disease was detected in five patients. All five had dyspnea, diffuse infiltrates, restrictive impairment and low single breath CO diffusing capacity (DLCOSB). Two of these patients underwent exercise testing and showed abnormalities consistent with lung disease (ventilatory limitation, excessive ventilation and increased dead space) as well as decreased VO2 max. and anaerobic threshold (AT). In contrast, in the other 13 patients, physical examination, chest radiographs and pulmonary function were normal (except for a low DLCOSB in one patient). Responses on exercise testing (performed in six of the 13 patients) were consistent with a circulatory impairment (decreased VO2 max. and AT). Our study found that <5% of patients with Type 1 GD have clinical interstitial lung disease. In addition, we found that some patients, without evident lung involvement, may experience limitations in physical exertion and are easily fatigued; this is attributable to impaired circulation.
Methylmalonic acidaemia is an inborn error of metabolism characterized by recurrent episodes of life-threatening ketoacidosis. With improved and intensive treatment, these patients are living into adulthood, but many experience late-onset disease complications such as chronic renal failure, chronic pancreatitis and osteopenia. We report the successful delivery of a healthy baby to a 20-year-old woman with vitamin B12-unresponsive methylmalonic acidaemia who has these late-onset manifestations of the disease and had plasma methylmalonic acid concentrations of 1900 mumol/L during the first trimester of pregnancy.
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