Table 1.
Causes of renal Fanconi syndrome to be considered for differential diagnoses of cystinosis
| Disorder (OMIM) | Gene | Inheritance | Protein | Key clinical/biochemical features |
|---|---|---|---|---|
| ARC syndrome | VPS33B | autosomal recessive | Vps33 | Arthrogryposis, cholestasis, dysmorphic features, ichtiosis, abnormal platelets, severe infections |
| Cystinosis | CTNS | autosomal recessive | Cystinosin | Failure to thrive, rickets, metabolic, acidosis, renal failure, photophobia |
| Dent’s diseasea | CLCN5 | X-linked recessive | Chloride channel 5 | LMW proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, renal failure |
| Fanconi–Bickel syndrome | SLC2A2 | autosomal recessive | Facilitative glucose transporter 2 (GLUT2) | Hepatorenal glycogen accumulation, hepatomegaly, rachitic and osteomalacia, mental retardation |
| Galactosaemia | GALT | autosomal recessive | Galactose-1-phosphate-uridyl-transferase | Hepatomegaly, liver disease, cataract, mental retardation |
| Glycogen Storage Disease Type 1 | G6PC | autosomal recessive | Glucose-6-phosphatase | Hypoglycemia, lactic acidosis and hyperlipidemia, hepatomegaly |
| Hereditary fructose intolerance | ALDOB | autosomal recessive | Aldose B | Fructose intolerance, growth retardation |
| I-cell disease (mucolipidosis II) | GNPTAB | autosomal recessive | N-acetylglucosamine-1-phosphotransferase | Dwarfism, contractures of large joints, coarse facial features, thickend skin and mucosae, mental retardation |
| Idiopathic Fanconi syndrome | Unknown | autosomal dominant autosomal recessive | Unknown | Isolated Fanconi syndrome |
| Lowe syndromea | OCRL1 | X-linked recessive | Phosphatidyl-inositol 4,5-biphosphate-5-phosphatase | Short stature, congenital cataract, mental retardation, seizures, cryptorchidism, arthropathy, elevated transaminases and creatine kinase |
| Metachromatic leukodystrophy | ARSA; PSAP | autosomal recessive | Arylsulfatase A; Prosaposin | Muscle wasting and weakness, spasticity, developmental regression |
| Mitochondrial diseaseb | Diverse | Diverse | Diverse | Diverse |
| Tyrosinaemia | FAHD2A | autosomal recessive | Fumaryl-acetoacetate hydrolase | Glomerulosclerosis, nephrocalcinosis, hepatomegaly, cirrhosis, rickets, growth retardation |
| Wilson disease | ATP7B | autosomal recessive | Copper-transporting ATPase (β subunit) | Kayser–Fleischer rings (cornea), hepatitis, cirrhosis CNS abnormalities |
aGlucosuria can be absent
bPatients with mitochondrial diseases can present with Fanconi syndrome. Among other reported genes, affected proteins involve cytochrome C oxidase, phosphoenolpyruvate carboxykinase or Acyl-CoA dehydrogenase