IllnessHypophosphataemia / rickets, differential diagnosis

NGS +

[Sanger]

In most cases, the symptomatology of hereditary hypophosphatemia/ rickets begins in early childhood. The features of the disorder vary widely, even among affected members of the same family. Mildly affected individuals show only hypophosphatemia. More severely affected children grow more slowly and may develop bone abnormalities (bowed leg, genu valgum, craniosynostosis, dental abnormalities), and adults develop osteomalacia. The most common form is X-linked dominant hypophosphatemic rickets (PHEX gene mutated); much rarer are X-linked recessive (CLCN5), autosomal dominant (FGF23, SLC34A1) and recessive forms (DMP1, ENPP1). Another rare disorder is hereditary hypophosphatemia/ rickets with hypercalciuria (SLC34A3 gene mutated). DNA diagnostic yields for hypophosphatemia/rickets are currently unknown; PHEX mutations comprise indels in up to >40%). The clinical diagnosis can in no way be ruled out by a negative molecular genetic result.

References: https://www.ncbi.nlm.nih.gov/books/NBK83985/

https://www.ncbi.nlm.nih.gov/books/NBK274564/

https://www.ncbi.nlm.nih.gov/books/NBK1480/

https://www.ncbi.nlm.nih.gov/books/NBK99494/

• Alias: Dominant hypophosphatemia with nephrolithiasis or osteoporosis, included
• Alias: Hereditary hypophosphatemic rickets with hypercalciuria, included
• Alias: Hypocalcemic vitamin D-resistant rickets, included
• Allelic: Arterial calcification, generalized, of infancy, 1 (ENPP1)
• Allelic: Cole disease (ENPP1)
• Allelic: Cystinosis, ocular nonnephropathic (CTNS)
• Allelic: Diabetes mellitus, non-insulin-dependent, susceptibility to (ENPP1)
• Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
• Allelic: Fanconi renotubular syndrome 2 (PHEX)
• Allelic: Hartsfield syndrome (FDGFR1)
• Allelic: Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Allelic: Jackson-Weiss syndrome (FGFR1)
• Allelic: McCune-Albright syndrome, somatic, mosaic (GNAS)
• Allelic: Nephrolithiasis, type I (CLCN5)
• Allelic: Nephrolithiasis/osteoporosis, hypophosphatemic, 1 (PHEX)
• Allelic: Obesity, susceptibility to (ENPP1)
• Allelic: Osseous heteroplasia, progressive (GNAS)
• Allelic: Pfeiffer syndrome (FGFR1)
• Allelic: Pituitary adenoma 3, multiple types, somatic (GNAS)
• Allelic: Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis (CLCN5)
• Allelic: Pseudohypoparathyroidism Ia (GNAS)
• Allelic: Pseudohypoparathyroidism Ib (GNAS)
• Allelic: Pseudohypoparathyroidism Ic (GNAS)
• Allelic: Pseudopseudohypoparathyroidism (GNAS)
• Allelic: Trigonocephaly 1 (FGFR1)
• Allelic: Tumoral calcinosis, hyperphosphatemic, familial, 2 (FGF23)
• ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Cystinosis, atypical nephropathic (CTNS)
• Cystinosis, late-onset juvenile or adolescent nephropathic (CTNS)
• Cystinosis, nephropathic (CTNS)
• Dent disease (CLCN5)
• Dent disease 2 (OCRL)
• Hypercalcemia, infantile, 2 (PHEX)
• Hypophosphatasia, adult (ALPL)
• Hypophosphatasia, childhood (ALPL)
• Hypophosphatasia, infantile (ALPL)
• Hypophosphatemic rickets (CLCN5)
• Hypophosphatemic rickets with hypercalciuria (SLC34A3)
• Hypophosphatemic rickets, AD (FGF23)
• Hypophosphatemic rickets, AR (DMP1)
• Hypophosphatemic rickets, AR, 2 (ENPP1)
• Hypophosphatemic rickets, XLD (PHEX)
• Lowe syndrome (OCRL)
• Odontohypophosphatasia (ALPL)
• Osteoglophonic dysplasia (FGFR1)
• Raine syndrome/osteosclerotic bone dysplasia, lethal (FAM20C)
• Rickets due to defect in vitamin D 25-hydroxylation (CYP2R1)
• Rickets, vitamin D-resistant, type IIA (VDR)
• Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic (HRAS, KRAS, NRAS)
• Tumoral calcinosis, hyperphosphatemic, familial, 3 (KL)
• Tyrosinemia, type I (FAH)
• Vitamin D-dependent rickets type 2B (HNRNPC)
• Vitamin D-dependent rickets, type 3 (CYP3A4)
• Vitamin D-dependent rickets, type I (CYP27B1)