Table 1 Differential diagnosis of cystinosis according to the most common presenting manifestations
From: Cystinosis: a review
| Presenting manifestations | Diseases | MIM | Gene | Protein | Other characteristic features at presentation |
|---|---|---|---|---|---|
| Proximal renal tubular acidosis | Tyrosinemia type I | 276700 | FAH | Fumarylacetoacetase | Hepatomegaly, mental retardation |
| Galactosemia | 230400 | GALT | Galactose-1-phosphate uridylyltransferase | Lethargy, jaundice, bleeding disorders, cataract, intellectual disability | |
| Hereditary fructose intolerance | 229600 | ALDOB | Aldolase B | Seizures, irritability, poor feeding, lethargy, liver disease | |
| Wilson disease | 277900 | ATP7B | Copper transporting P-type ATPase | Liver disease, neuropsychiatric manifestations, Kayser-Fleischer ring in the cornea | |
| Lowe syndrome | 309000 | OCRL | Phosphatidylinositol 4,5-diphosphate 5-phosphatase | Congenital cataract, glaucoma, intellectual disability, hypotonia, seizures, behavioral problems | |
| Dent’s disease | 300009 | CLCN5 | Chloride Channel Protein number 5 | Low molecular weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, progressive renal failure | |
| Mitochondrial disorders: | |||||
| - Leigh syndrome | 256000 | COX10 | Cytochrome C oxidase assembly protein | Encephalopathy, myopathy, respiratory istress, deterioration of cognitive function | |
| - Gracile syndrome | 603358 | BCS1L | S. cerevisiae bcs1 protein homolog | Severe lactic acidosis, hypoglycemia, cholestasis, iron overload | |
| - HUPRA syndrome | 613845 | SARS2 | Seryl-t-RNA synthetase | Hyperuricemia, pulmonary hypertension, renal failure, alkalosis | |
| - Mitochondrial DNA depletion syndrome 8 | 612075 | RRM2B | Ribonucleotide reductase small subunit 2 like | Neonatal hypotonia, lactic acidosis, neurologic deterioration | |
| - Mitochondrial DNA depletion syndrome 13 | 615471 | FBXL4 | Leucine rich repeat protein 4 | Hypotonia, lactic acidois, microcephaly, congenital cataract | |
| Heavy metal toxicity: Lead, cadmium | ---------- | ----------- | --------------------------------------- | Anemia, abdominal pain, encephalopathy, osteomalacia, neurological manifestations | |
| Hypophosphatemic Rickets | Hypophosphatemic nephrolithiasis/osteoporosis I | 612286 | SLC34A1 | Sodium-phosphate cotransporter, member 1 | Nephrolithiasis, osteoporosis, multiple fractures |
| Hypophosphatemic nephrolithiasis/osteoporosis II | 612287 | SLC9A3R1 | Sodium/hydrogen exchanger regulatory factor 1 | Nephrolithiasis, osteoporosis, hypocalcemia, hypoparathyroidism | |
| Autosomal dominant hypophosphatemic rickets | 193100 | FGF23 | Fibroblast growth factor 23 | Fatigue, bony pains, bone deformities | |
| Autosomal recessive hypophosphatemic rickets | 241520 | DMP1 | Dentin matrix acidic phosphoprotein 1 | Retarded skeletal growth, abnormal mineralization | |
| Hereditary hypophosphatemic rickets with hypercalciuria | 241530 | SLC34A3 | Sodium-phosphate cotransporter, member 3 | Elevated serum 1,25-dihydroxy vitamin D levels, hypercalciuria, osteomalacia, nephrolithiasis, nephrocalcinosis | |
| Vitamin D dependent rickets type I | 264700 | CYP27B1 | 25-hydroxyvitamin D3-1-alpha-hydroxylase | Hypotonia, muscle weakness, seizures | |
| Vitamin D dependent rickets type II | 277440 | VDR | vitamin D receptor | Alopecia, hypocalcemia, secondary hyperparathyroidism, osteomalacia, osteitis fibrosa cystica | |
| Stunted growth | Cystic fibrosis | 219700 | CFTR | Cystic fibrosis transmembrane conductance regulator protein | Frequent chest infections, pancreatic insufficiency |
| Chronic malnutrition | ---------- | ----------- | --------------------------------------- | Fatigue, anemia, poor cognitive function, behavioral changes, history of poor socioeconomic standard | |
| Hormonal causes | |||||
| - Hypothyroidism | ---------- | ----------- | --------------------------------------- | Lethargy, fatigue, dry skin, cold intolerance, constipation, mental subnormality | |
| - GH deficiency | ---------- | ----------- | --------------------------------------- | Short stature with general good health, normal intelligence | |
| Familial | ---------- | ----------- | --------------------------------------- | Family history |