Genetic causes of proximal tubular defects, cystinosis, tyrosinaema type 1, galactosaemia and Lowe's syndrome cause generalised proximal tubular dysfunction (Fanconi syndrome), Dent's disease causes a degree of proximal tubular dysfunction with nephrolithiasis, while cystinuria purely causes cysteine urinary stones.11 14 20
| Disease | Gene | Gene product | Inheritance | Extra-tubular manifestations | Phenotype OMIM number |
|---|---|---|---|---|---|
| Cystinosis | CTNS | Cystinosin | Autosomal recessive | Fair hair and complexion, hypothyroidism, photophobia (corneal cysteine crystals) | 219800 |
| Tyrosinaemia type 1 | FAH | Fumaryl acetoacetate hydrolase | Autosomal recessive | Hepatomegaly, progressive liver dysfunction, peripheral neuropathy | 276700 |
| Galactosaemia | GALT | Galactose-1-phosphate uridyltransferase | Autosomal recessive | Cataracts, hepatomegaly, progressive liver dysfunction, seizures, hypoglycaemia | 230400 |
| Lowe's syndrome | OCRL | Phosphatidylinositol 4,5-bisphosphate 5-phosphatase | X-Linked | Cataracts, hypotonia, developmental delay | 309000 |
| Dent's disease | CLCN5 | Chloride channel | X-Linked | Nephrocalcinosis, nephrolithiasis | 300009 |
| Cystinuria type 1 | SLC3A1 | SLC3A1 amino acid transport protein | Autosomal recessive | Nephrolithiasis (cystine stones) | 220100 |
OMIM, Online Mendelian Inheritance in Man.