Table 1 Differential diagnosis of cystinosis according to the most common presenting manifestations

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

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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

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Fatigue, anemia, poor cognitive function, behavioral changes, history of poor socioeconomic standard

Hormonal causes

- Hypothyroidism

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Lethargy, fatigue, dry skin, cold intolerance, constipation, mental subnormality

- GH deficiency

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Short stature with general good health, normal intelligence

Familial

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Family history