Cystinosis, Late-Onset Juvenile Or Adolescent Nephropathic Type

A number sign (#) is used with this entry because adolescent nephropathic cystinosis is caused by mutation in the gene encoding cystinosin (606272), which maps to chromosome 17p13. See also 219800 for general information about nephropathic cystinosis and the infantile type of the disorder.

Clinical Features

Adolescent nephropathic cystinosis manifests itself first at age 10 to 12 years with proteinuria due to glomerular damage rather than with the manifestations of tubular damage that occur first in infantile cystinosis. There is no excess amino aciduria and stature is normal. Photophobia, late development of pigmentary retinopathy, and chronic headaches are features. White cells show high cystine content in heterozygotes for this form of cystinosis, just as they do in infantile cystinosis. Spear et al. (1971) described glomerular changes in renal biopsies from a case of late-onset nephropathic cystinosis. Clinically the disorder shows a slowly progressive glomerular insufficiency rather than the prominent Fanconi syndrome, electrolyte and water disturbances, growth arrest, and rickets typical of infantile cystinosis. The patient was the only affected person in the family and the parents were not related (as one would expect if juvenile cystinosis is the genetic compound of infantile cystinosis and adult cystinosis).

Molecular Genetics

Attard et al. (1999) identified a mutation in the CTNS gene (606272.0008) in a patient with late-onset juvenile nephropathic cystinosis.

Thoene et al. (1999) described 2 sibs in Taiwan with intermediate cystinosis who had linear growth and weight gain within 2 standard deviations of the mean for their ethnic group until the ages of 13 and 14 years when their plasma creatinine concentrations were 1.2 mg per deciliter and 3.3 mg per deciliter, respectively. They were found to be homozygous for a missense mutation in the CTNS gene substitution of lysine for the conserved asparagine at position 323 (N323K; 606272.0016). Presumably, this mutation allowed for some residual cystine transport, accounting for the mild clinical presentation.

In 2 unrelated Spanish patients with juvenile-onset cystinosis, Macias-Vidal et al. (2009) identified compound heterozygosity for a missense mutation (S139F; 606272.0018) and truncating mutations (606272.0004 and 606272.0005, respectively). The S139F mutation had previously been identified in a patient with 'nonclassic' cystinosis (see 219800), with onset before age 7 years but a milder course of disease than the infantile nephropathic form, by Attard et al. (1999), who suggested that the mutation might allow production of functional protein or be located in a region of cystinosin that was not functionally important.