Order and Disorder in Pulmonary Function
Authors: W. M. Arnott
Journal: BMJ (1955)

BJouRNL a block in protein synthesis, so that the amino-acids colect in the body fluids; these are excreted in excess in the urine, and cystine, owing to its insolubility, is deposited intra- cellularly.Clinical Picture.-It is only possible for me to outline briefly the wide variations in clinical signs which may be produced.They have received detailed attention from Mc- Cune et al. (1943) and Bickel et al. (1952).The first evidence of the disease may appear in infancy, usually after the first six months of life, as an acute disorder with acidosis, dehy- dration, thirst, and polyuria, anorexia, vomiting, constipa- tion, pyrexial bouts, and failure to thrive.In fact, it may not be clinically distinguishable from hyperchloraemic acid- osis or hypercalcaemia, although in these diseases there is no amino-aciduria or glycosuria.In older children there will be dwarfism, and often bone deformities, vitamin-D refractory rickets, or pathological fractures.A quite char- acteristic but not constant sign is photophobia, which is caused by deposits of cystine crystals in the cornea, iris, and conjunctiva.This form of the disease must be clearly separated from the so-called " renal rickets" of chronic glomerular insufficiency, in *hich amino-aciduria, glyco- suria, and cystine storage do not occur.Chemical Picture.-Bickelet al. (1952) point out that no single chemical change is constantly found in cases of this disease.The typical findings in the urine, which is alkaline when passed, are albuminuria, excess amino-aciduria, glyco- suria, and hyperphosphaturia.Several specimens may have to be tested by sensitive methods such as paper chromato- graphy (Dent, 1946) before these features are revealed.Up to twenty amino-acids may be excreted in excess, especially proline, leucine, valine, lysine, serine, cystine, threonine, glutamine, and alanine.The typical blood changes are lowered plasma bicarbonate due to metabolic acidosis, low plasma phosphorus, and low serum potassium levels.The blood urea may rise in the course of the disease.As renal failure supervenes there may develop hyperphosphataemia and hypocalcaemia, when the blood chemistry comes to resemble that seen in " renal rickets " due to glomerular inadequacy.Diagnosis.-Thedemonstration of cystine storage should be regarded as the final proof of Lignac-Fanconi disease.This may be achieved in various ways: (1) Crystalline deposits may be seen in the eye with the slit-lamp.They may be identified as cystine by x-ray diffraction photography of a conjunctival biopsy specimen. (2)Thick bone-marrow smears may be examined for cystine crystals after fixation in absolute alcohol and staining with a solution of 0.5 g. basic fuchsin in 100 ml. of 50% alcohol.Cystine is dis- solved out of tissues by routine fixatives and stains.(3) Microscopical examination of a lymph node.Prognosis.-In the acute infantile form of the disease death occurs from acidosis and hypopotassaemia, often aggravated by infection.The older children die ultimately of chronic progressive renal failure.Treatment.-Healing of the rickets can be achieved by massive doses of calciferol (50,000 to 600,000 units daily).Acidosis should be corrected by Shohl's solution.If there is a lowered serum potassium, some of the sodium citrate may be replaced by the potassium salt.Strict blood chemical control is necessary.We cannot yet talk in terms of cure, but life can be prolonged along these lines. Conclusion