Endocrine Abstracts

JOINT3295

Objective: To report the clinical features and management of a child with familial hypomagnesemia and hypercalciuric nephrocalcinosis (FHHNC) in order to enhance awareness of this condition. Methods: The medical history, laboratory tests, and treatment process of one FHHNC patient were analyzed, and genetic testing was performed on the proband, parents, and elder brother. Results: An 11-year-old girl presented with "growth retardation, polydipsia, and polyuria for over seven years." Seven years prior, she gradually exhibited growth retardation accompanied by excessive drinking, consuming 3-4 liters of water daily, polyuria, and nocturia, with two episodes of febrile convulsions (details unknown). On examination, her height was 117cm (-4.72SD), weight 21kg, presenting with disproportionate short stature, breast Tanner stage B1, no abnormalities in the heart or lungs, and bilateral X-shaped legs. Her parents were healthy, non-consanguineous, and there were no similar diseases reported in the family. Laboratory tests revealed serum calcium 1.5mmol/l↓, serum phosphorus 0.95mmol/l↓, alkaline phosphatase 1151u/l↑, parathyroid hormone 418pg/ml↑, 25-hydroxyvitamin D 17.97ng/ml↓, 1.25-hydroxyvitamin D 58.8pg/ml, serum magnesium 1.11mmol/l↓, urinary calcium 8.5mmol/24h↑, urinary phosphorus 3.6mmol/24h, serum creatinine 69.2umol/l↑, urinary alpha-1 microglobulin 39.8mg/l↑, urinary beta-2 microglobulin 29.3mg/l↑, urinalysis showing leukocytes 2+, renal ultrasound indicating nephrocalcinosis, cranial CT scan showing bilateral basal ganglia high-density shadows, and X-rays showing slight expansion and roughness at the distal metaphysis of the radius and ulna. Genetic testing identified a splice site mutation c.427+5G>A (homozygous) in the CLDN16 gene [Chr3(GRCh37):g.190120233G>A], which her parents and brother carried as heterozygous carriers without phenotypic expression. The diagnosis for the patient was 1. FHHNC; 2. Urinary tract infection.

Conclusion: FHHNC is a rare autosomal recessive disorder characterized by excessive renal excretion of magnesium and calcium, bilateral nephrocalcinosis, and progressive chronic renal failure. The disease often presents with severe renal impairment before diagnosis, with symptomatic treatment being the main approach, including low-dose hydrochlorothiazide, potassium citrate, and calcium-magnesium tablets to significantly improve hypomagnesemia and hypercalciuria. The prognosis is poor, with approximately one-third of patients presenting with chronic kidney disease at diagnosis, requiring renal transplantation for end-stage renal failure. Genetic testing can confirm the diagnosis. Routine magnesium blood tests are recommended for children with short stature. Clinicians should consider FHHNC in patients presenting with short stature, polyuria, hypocalcemia, hypomagnesemia, and nephrocalcinosis. This case reports a novel CLDN16 gene mutation site in China.

Keywords: Short Stature, Familial Hypomagnesemia and Hypercalciuric Nephrocalcinosis, CLDN16 Gene, Renal Failure, Hypocalcemia