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Five inherited disorders of tyrosine metabolism are known, depicted in Fig. 18.1. Hereditary tyrosinaemia type I is characterised by progressive liver disease and renal tubular dysfunction with rickets. Hereditary tyrosinaemia type II (Richner-Hanhart syndrome) presents with keratitis and blisterous lesions of the palms and soles. Tyrosinaemia type III may be asymptomatic or associated with mental retardation. Hawkinsinuria may be asymptomatic or presents with failure to thrive and metabolic acidosis in infancy. In alkaptonuria symptoms of osteoarthritis usually appear in adulthood. Other inborn errors of tyrosine metabolism include oculocutaneous albinism caused by a deficiency of melanocyte-specific tyrosinase, converting tyrosine into DOPA-quinone; the deficiency of tyrosine hydroxylase, the first enzyme in the synthesis of dopamine from tyrosine; and the deficiency of aromatic L-amino acid decarboxylase, which also affects tryptophan metabolism. The latter two disorders are covered in ▸ Chap. 29.

Cystinosis is a generalized lysosomal storage disease classified into three clinical phenotypes, of which the nephropathic or infantile form is by far the most frequent. The first symptoms start at about 6 months of age with anorexia, polyuria, failure to thrive and are manifestations of a Fanconi proximal renal tubulopathy. The natural history is that of end stage renal disease between 6 and 12 years. Survival beyond this age is associated with the development of extrarenal complications in eyes, thyroid, gonads, endocrine pancreas, muscle and central nervous system. An intermediate or juvenile onset form, and a benign or adult form limited to the eyes, are caused by lesions of the same gene. The lysosomal cystine accumulation leads to cellular dysfunction of many organs without a clear mechanism. The disease is caused by mutations in the gene coding for , a lysosomal carrier protein. The diagnosis is ascertained by measurement of cystine in leukocytes. Treatment is both supportive and specific, the latter based on cysteamine, which effectively decreases cystine accumulation.

Primary hyperoxalurias (PH) are rare diseases which are characterized by overproduction and accumulation of oxalate in tissues.

caused by deficiency or mistargeting of alanine: glyoxylate aminotransferase (AGT) in liver peroxisomes is the most frequent and most severe form. Deposits of calcium oxalate crystals in the kidney lead to stones, nephrocalcinosis and deteriorating kidney function, while bone disease is the most severe extrarenal involvement. Careful conservative treatment (high fluid intake, calcium-oxalate crystallization inhibitors, and pyridoxine) should be started early as it may prolong kidney survival. Liver and kidney transplantation are the final current options. Hyperoxaluria and hyperglycoluria are indicative of PH1.

, caused by glyoxylate-reductase (GR) deficiency in the liver and other tissues, is less frequent and less severe, and treatment less demanding. Hyperoxaluria without hyperglycoluria and increased urinary excretion of L-glycerate differentiate it from PH1.

In addition, there are isolated reports of PH without either AGT or GR deficiency, so that it is likely that there is at least another form of PH (PH3) yet to be explained.