Human biochemical genetics / by H. Harris.

  • Harris, Harry, 1919-1994.
Date:
1966
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Human biochemical genetics / by H. Harris. Source: Wellcome Collection.

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    THE FANCONI SYNDROME 87 It is often referred to as cystinosis. Although this was first recognised in post-mortem examinations, it was later found that it could be detected during life by the demonstration of cystine crystals in aspirated bone marrow and lymph nodes removed by biopsy, or by slit lamp examination of the cornea. Affected children usually do quite well for the first few months of life and then may present because of vomiting failure to thrive, or polyuria. In other cases the first indication of the disease is a severe resistant type of rickets with dwarfing and concomitant deformities. The prognosis is poor and death usually occurs before puberty. The amounts of cystine deposited in the tissues in such cases may be very considerable. Dent and Fowler (зо), for example, found quantities of the order of 300 and 900 mg. of cystine per g. tissue total nitrogen in hver and spleen respectively as compared with control values of the order of 2 or 3 mg. per g. nitrogen. There is obviously a very gross disorder in the handling of cystine and possibly of other more soluble aminoacids by the tissues, but the nature of this is at present quite obscure. Despite the profound disturbance in aminoacid metabolism implied by this widespread deposition of cystine in the tissues, the amino¬ aciduria which includes an increased cystine output as one of its components appears to be essentially renal in origin. The amino- nitrogen level in the plasma is usually within normal limits and the amino-nitrogen clearance is significantly raised (3i). It has indeed been plausibly argued that many of the features of the disorder can be attributed to a gross defect in the proximal convoluted tubules of the kidney resulting in imperfect reabsorption of many aminoacids, glucose, phosphate, bicarbonate, and perhaps potassium from the glomerular filtrate. A low renal threshold for phosphate, for example, could account for the hypophosphataemia, and this could be regarded as determining the peculiarities in bone formation which are similar in type to those found in other forms of Vitamin D resistant rickets and osteomalacia, where inadequate tubular reabsorp¬ tion of phosphate seems to occur without any associated renal aminoaciduria. Support for this concept of a defect in tubular function has been provided by the elegant microdissections of nephrons from kidneys of such patients carried out by Darmady and his colleagues (32). They have found a peculiar and characteristic morphological abnormality of the proximal tubule. This is shorter than normal and is joined to