An Unusual Presentation of Diabetic Ketoacidosis in Familial Hajdu-Cheney Syndrome: A Case Report
A 21-yr-old Korean man was referred to the Department of Endocrinolgy and Metabolism from his primary physician for proper management of hyperglycemia and metabolic impairment on September 21 of year 2012. During the 2 yr since the patient's discharge from military service he had lost approximately 10 kg in body weight. At admission, he complained of polyuria and polydipsia. He had no known medical past history or fracture history, but his mother and elder brother had been diagnosed with HCS along with osteoporosis and multiple compression fractures of the spine (, ). On admission the patient showed stable vital signs and alert mental status. Blood pressure was 107/63 mmHg and pulse rate was 59/min. His height was 175 cm (50 percentile) and weight was 55 kg (10 percentile). The physical examination revealed dysmorphic features, such as marked eyebrow, which was similar to that of his brother in whom HCS had been diagnosed at the age of 20. Short and clubbed fingers were found (). Laboratory investigations revealed hemoglobin of 11.8 g/L, total white blood cell count of 4,800/µL (73% neutrophils). Serum biochemistry, hormones, and bone markers were tested (). No antibody to glutamic acid decarboxylase was detected. Arterial blood gas analysis revealed metabolic acidosis (pH 7.318, base excess -15.2 mM/L, bicarbonate 8.6 mM/L) with incomplete respiratory compensation (pCO2 17.2 mmHg). Urine analysis revealed that specific gravity of 1.024, strong positive in glucose and ketone bodies. A chest X-ray was normal and electrocardiography showed normal sinus rhythm. After an initial treatment for DKA, evaluations for metabolic bone disease were performed. Laboratory findings showed follicle-stimulating hormone 0.7 IU/L, luteinizing hormone 1.2 IU/L, testosterone 2.25 ng/mL (7.8075 nM/L), osteocalcin 8.9 ng/mL (1.5219 nM/L), 25-hydroxy-Vitamin D 5.7 ng/mL (14.2272 nM/L), intact parathyroid hormone <8 ng/L, and urine N-telopeptide 151 nM/mM creatinine. A hand X-ray revealed brachydactyly of the 5th finger of both hands (). Thoracolumbar spine X-ray revealed a fracture of T12 and L3 (). Skull X-ray revealed wormian bone (). Bone mineral density revealed osteoporosis (L1-L2 0.826 g/cm2, T-score -2.6, Z-score -2.5, total femur 1.203 g/cm2, T-score 2.0, Z-score 1.8) (). To confirm the diagnosis of HCS, DNA sequencing was conducted. The sequence analysis revealed that the patient and his mother had a heterogenetic mutant allele in the NOTCH2 gene (c.6443T>G) () leading to an amino acid substitution from a leucine to a stop codon (p.Leu2148*) (). The patient was diagnosed with HCS and DKA. To manage DKA, fluid resuscitation and insulin treatment was initiated. His metabolic acidosis normalized. Since then the patients has been treated with 1,250 mg of calcium carbonate and 1,000 IU of cholecalciferol per day under the diagnosis of osteoporosis and compression fracture due to HCS, and with 5 units of basal insulin and 7 units of pre-prandial insulin injection for type 1 DM. Laboratory analyses conducted during the course of treatment showed improved HbA1c (7.5%) and fasting glucose (175.8 mg/dL or 9.768 mM/L).