Context: Mutations of cytochrome P450 24 subfamily A member 1 (CYP24A1) gene are associated with Idiopathic Infantile Hypercalcemia (IIH), a disease recently related to vitamin D catabolism impairment.
Aim of the study: Report of clinical and biochemical features of a large family with a novel mutation of CYP24A1.
Methods: We performed dosage of total calcium, ionized calcium, 24 h urinary calcium, PTH, 25-OH-Vitamin D (25-OH-D), and 2425 Vitamin D, genetic analysis of CYP24A1 and abdomen ultrasound in the proband, a 44 year old man, and in first-degree relatives (Mother, Father, Sister and Two sons). Vitamin D metabolites were analyzed using liquid chromatography mass spectrometry at Queens University Laboratory (Kingston, Canada).
Results: The proband showed high levels of total calcium, 25-OH-D, 1,25-(OH)2-D and low levels of PTH, 24,25-(OH)2D3 and 1,24,25-(OH)3D3. 25-OH-D/24-25-OH-D ratio was high (500.5). Abdomen ultrasound showed bilateral nefrolitiasis. Genetic analysis revealed a novel homozygous mutation. In first-degree relatives, serum calcium and 25-OH-vitamin D were in the upper limit of normal range and PTH low. The 25-OH-D/24-25-OH-D ratio was normal. Abdomen ultrasound showed nefrolitiasis only in the sister. Genetic analysis confirmed the mutation in heterozygosity in each member.
|Family members||CYP24A1 Mutation||*Ca2+ (mmol/L)||*PTH (ng/L)||25-OH-D (ng/mL)||24,25-(OH)2D3 (ng/mL)||*25D3/24,25D3||1,24,25-(OH)3D3 (pg/mL)||1,25-(OH)2D3 (pg/mL)||Nephro-lithiasis|
|Proband (M 44 yr)||c.667 A>T p.Arg223 Homozygous||1.34||6||71.89||0.14||500.5||<2||68.2||yes|
|Sister (54 yr)||c.667 A>T p.Arg223 Eterozygous||1.26||14||32.26||1.54||20.6||19.7||56.6||yes|
|Son (13 yr)||c.667 A>T p.Arg223 Eterozygous||1.33||12||37.55||1.83||20.4||15.6||97.2||no|
|Son 2 (11 yr)||c.667 A>T p.Arg223 Eterozygous||1.37||20||40.59||1.53||26.3||10||70.4||no|
|Father (85 yr)||c.667 A>T p.Arg223 Eterozygous||n.a.||n.a||38.95||1.15||33.6||10.8||41.6||no|
|Mother (82 yr)||c.667 A>T p.Arg223 Eterozygous||n.a.||n.a||48.93||2.37||20.5||17.2||38.3||no|
|n.a.: not available*Ca2+: normal range 1,121,32 mmol/L * PTH: normal range 8-40 ng/L *25D3/24,25D3: normal range < 30.|
Conclusions: We report the biochemical and clinical features of a family with a novel CYP24 A1 mutation. Preliminary data suggest that the new mutation is associated with a mild phenotype. However, genetic and environmental factors could contribute in the clinical outcome.
18 May 2019 - 21 May 2019