4Recent progress in our knowledge of cystinosis
| Autor: | Jerry A. Schneider, Wolfgang A. Kroll |
|---|---|
| Rok vydání: | 1974 |
| Předmět: |
medicine.medical_specialty
Pathology Conjunctiva Metabolic disorder Cystine Fanconi syndrome Biology medicine.disease Biochemistry chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry Renal tubular dysfunction Nephropathic Cystinosis Internal medicine Cystinosis medicine Kidney disease |
| Zdroj: | Clinics in Endocrinology and Metabolism. 3:57-69 |
| ISSN: | 0300-595X |
| DOI: | 10.1016/s0300-595x(74)80025-3 |
| Popis: | Summary Cystinosis is a recessively inherited metabolic disorder characterised biochemically by a high intracellular content of free (non-protein) cystine which results in crystal deposition in the cornea, conjunctiva, bone marrow, lymph nodes, leucocytes and other internal organs. The primary abnormal gene product which leads to the cystine accumulation is unknown. Clinical expression ranges widely from one family to another with three different forms of cystinosis having been clearly delineated. The most severe form, nephropathic cystinosis, is characterised by generalised renal tubular dysfunction (the Fanconi syndrome) and by progressive glomerular damage which leads to end-stage kidney disease within the first decade of life. In other families, cystinosis is diagnosed by an ophthalmologist who sees tinsel-like refractile opacities in the cornea and conjunctiva during a slit lamp examination. Although these patients generally have cystine crystals in both their conjunctiva and bone marrow, their renal function is completely normal. In a third type of cystinosis, there is both renal tubular and glomerular damage, but clinical symptoms are not noted until about five years of age. This has been called the intermediate or late-onset type of cystinosis. The intracellular content of free (non-protein) cystine is about 100 times normal in white blood cells and cultured skin fibroblasts from patients with nephropathic cystinosis and about 30 times normal in these tissues from patients with benign cystinosis. The values in patients with the late-onset type fall between these ranges. Heterozygotes for all three types show modest increases in cystine concentration. All three forms of cystinosis appear to be transmitted by an autosomal recessive pattern of inheritance. The fact that all three types of cystinosis run true in families demonstrates the genetic heterogeneity of this disorder. Experimental treatment with a diet restricted in cystine and methionineand by administration of d -penicillamine failed to influence the course of the disease. Dithiothreitol has been suggested as a useful form of therapy but it is still in an experimental stage. At present, renal homotransplantation in children with nephropathic and intermediate types of cystinosis appears to offer the best opportunity for extended survival and is the only effective treatment in terminal renal failure. Prenatal diagnosis of nephropathic cystinosis has been accomplished by measurement of the elevated cystine content in cultured amniotic fluid cells by a pulse-labelling technique, making preventive control of the disease possible. Cystinotic fibroblasts have been fused with non-cystinosic cells by the technique of somatic cell hybridisation. In every instance, the hybrid cells had a normal cystine content. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|