ESPN 51th Annual Meeting

ESPN 2018


 
CLINICAL AND GENETIC FEATURES OF IDIOPATHIC INFANTILE HYPERCALCEMIA, TYPE 1 IN CHILDREN
Svetlana Papizh 1 Larisa Prikhodina 1

1- RESEARCH AND CLINICAL INSTITUTE OF PEDIATRICS, RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY
 
Introduction:

Idiopathic infantile hypercalcemia, type 1 (IIH1) (OMIM # 143880) is a rare autosomal recessive disorder characterized by hypercalcemia, hypercalciuria, failure to thrive, polyuria and dehydration, and/or nephrocalcinosis (NC). IIH1 caused by mutation in the CYP24A1 gene (OMIM #126065) encodes 1,25(OH)D3-24-hydroxylase, a key enzyme responsible for the catabolism of active vitamin D. The aim of the study was to evaluate the clinical features and molecular basis of IIH1 in Russian children.

 

Material and methods:

6 children (3M/3F) with IIH1 from unrelated families were examined. The median age of patients at the first follow up was 2.5 (IQR: 1.0; 5.0) years. Molecular genetic analysis was performed in all children using by next generation sequencing (NGS).

 

Results:

The most prevalent features of IIH1 were medullary NC in 6/6 (100%) patients and hypercalcemia in 5/6 (83.3%). Decreased serum PTH level was found in 4/6 (66.7%) children. Increased serum alkaline phosphatase (ALP) activity had 3/6 (50%) patients, all children aged 1 year. All children with IIH1 had normal serum level of 1,25(OH)D3. Hypercalciuria revealed only in 2/6 (33.3%) subjects with IIH1. Decreased eGFR had all patients, including CKD-2 in 5/6 (83.3%) and CKD-3 in 1/6 (16.7%) of patients. NGS identified previously reported mutations in the CYP24A1 gene c.1186C>T in 5 cases (in 2 children in homozygous and in 3 cases in heterozygous state), and 3 novel mutations c.233G>T, c.475C>T, c.442T>C in 2 cases (Table).

 

Table.

Patients

Gender

Age, y

Ca2+/ Ca total, mmol/l

PTH, pg/ml

eGFR, ml/min/1.73 m2

Ca/Cr, mmol/mmol

Mutations

#1

m

1

1.35/2.56

14.5

67.9

0.75

c.1186C>T*

#2

f

1

1.45/2.71

13.3

63.7

1.1

c.1186C>T*

#3

m

1

1.36/2.9

5.9

55.5

0.7

c.475C>T**

c.442T>C**

#4

f

4

1.37/2.55

16.7

75.2

1.28↑

c.1186C>T

c.428_430delAAG

#5

f

5

1.29/2.32

15

73.0

1.64↑

c.1186C>T

c.233G>T**

#6

m

5

1.34/2.33

28

85.2

0.55

c.1186C>T

c.428_430delAAG

* homozygous

**novel mutation

 

 

Conclusions:

The present study demonstrated that most prevalent features of IIH1 in our children were medullary NC, hypercalcemia, and decreased eGFR. A greater awareness of IIH1 phenotypes will increase clinical suspicion in patients presenting with NC or hypercalciemia. Testing for mutations in CYP24A1 gene can establish a definitive diagnosis and clinical management with minimizing vitamin D intake to prevent effects of vitamin D toxicity and dietary advice.