ESA-SRB-AOTA 2019

Severe Salt and Water Imbalance in a Woman with Primordial Dwarfism (#609)

Jasmine Wintour 1 , Eleanor Warwick 2 , Johanna Kuehn 1 , Thida Myint 2 3 , Himanshu Goel 2 4 , Katie Wynne 1 2
  1. Department of Diabetes & Endocrinology, John Hunter Hospital, Newcastle, NSW, Australia
  2. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  3. Department of Nephrology, John Hunter Hospital, New Lambton Heights, NSW, Australia
  4. Hunter Genetics, Waratah, NSW, Australia

A 53-year old woman of height 101cm and weight 15kg, presented with confusion, and serum sodium level 107mmol/l. She had a generalized seizure and was given two 25ml boluses of hypertonic 3% saline. She was transferred to ICU and received an infusion of 3% saline at 5mls/hour, calculated using the Adrogué-Madias equation.1 She required two boluses of 100mls 0.9% saline when hypotensive (70/40mmHg) with low-normal urine output (5-10mls/hour). Collateral history revealed IgM paraproteinaemia and cold agglutinin disease.

Investigations demonstrated potassium 3.8mmol/l, urea 2.3mmol/l, creatinine 47umol/l, ACTH 4.9pmol/l, cortisol 278nmol/l, TSH 1.77mIU/l, T4 9.5pmol/l, LH 5.7IU/l, FSH 23.4IU/l, estradiol <100pmol/l, prolactin 29mU/l, GH 0.4mU/l, IGF-1 28ug/L. She commenced hydrocortisone 20mg intravenously three-times daily for anterior pituitary deficiency. Hydrocortisone triggered a transient diuresis of 30-40mls/hour. She received 100mls of 5% dextrose over two hours to prevent sodium overcorrection. Her sodium level reached 115mmo/l on day 2 and 125mmol/l on day 3.

MRI pituitary confirmed a hypoplastic gland with preserved posterior bright spot. Despite stress dose hydrocortisone 8mg three times daily, renal excretion of sodium remained inappropriately elevated, with excess loss of potassium, phosphate, calcium, glucose and protein consistent with tubular dysfunction. Transabdominal ultrasound demonstrated a small uterus and ovaries with two asymptomatic renal calculi. She was discharged day 7 on Hydrocortisone 4mg waking, 2mg noon, 2mg 4pm, oral sodium 2.4g/day and potassium chloride 20mmol/day, with a sodium level of 136mmol/l and normal serum potassium

A diagnosis of DNA Polymerase Epsilon Deficiency2 due to biallelic pathogenic genetic variants in POLE caused her extreme growth disorder starting in utero. 2,3 Clinical features include short stature, microcephaly, immune dysfunction, micrognathia, a thin nose, wide neck and posteriorly rotated ears. Pituitary failure is reported and in this case became clinically apparent later in life.2 Profound hyponatraemia was complicated by an accompanying renal tubular defect.

  1. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med 2000;342:1581–9.
  2. Logan CV, Murray JE, Parry DA, Robertson A, Bellelli R, Tarnauskaite Z, Challis R, Cleal L, Borel V, Fluteau A et al. DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency. The American Journal of Human Genetics. 2018 103, 1038-1044.
  3. Thiffault I, Saunders C, Jenkins J, Raje N, Canty K, Sharma M, Grote L, Welsh HI, Farrow E, Twist G et al. A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes. BMC Med Genet 16, 31.