Table 1 Timeline
Dates | Relevant Past Medical History and Interventions | ||
|---|---|---|---|
13/11/2016 | A full-term AGA neonate, by third-degree cousins, born by spontaneous vaginal delivery, after a normal pregnancy. No remarkable obstetric and family history. Discharged home at the 3rd DOL. | ||
Dates | Summaries from Initial and Follow-up Visits | Diagnostic Testing (including dates) | Interventions |
21/11/2016 | During paediatrician’s visit because of poor feeding and lethargy, the neonate had a cardiorespiratory arrest. | High quality cardiopulmonary resuscitation (30:2, single rescuer) for 3 minutes with reappearance of vital signs. | |
21/11/2016 | Admission at NICU-Policlinico of Bari (Italy): significant weight loss, lethargy, hypotonia and absent tendon reflexes. | Severe hypercalcemia (28.7 mg/dl; RR: 8.6 ± 11.8 mg/dl), high serum alkaline phosphatase activity (663 U/L; RR: 105÷410 U/L), hyperparathyroidism (PTH 465 pg/ml; RR: 6.5÷36.8 pg/ml), hypophosphatemia (2 mg/dl; RR: 3.1÷7.7 mg/dl), normal magnesium (2.2 mg/dl; RR 1.8–2.4 mg/dl), normal 25-hydroxyvitamin D (33.1 pg/ml; RR: 19.8 ± 79.3 pg/ml). | Low calcium intake (85 mg/day), intravenous fluid hyperhydration (glucose solution 8% with aminoacids and physiologic solution - 220 ml/kg/day), Furosemide (2 mg/kg/day), Clodronate (1 mg/kg/day): No response (after 7 days of therapy) |
26/11/2016 | Persistent severe hypercalcemia, polyuria, dehydration, hypotonia, bone changes and failure to thrive. | Total body X-rays (skeletal undermineralization, subperiosteal bone resorption). ECG (anomalies of the recovery phase,“QT stretching”). Abdominal, cerebral and cardiac ultrasound (normal). Parathyroid glands Ultrasound: glands not detectable. | Cinacalcet (0.4 mg/kg/day): No response (after 2 weeks of treatment). No adverse reactions. |
05/12/2016 | Both parents were clinically and biochemically normal. | Genomic DNA of proband and parents extracted from peripheral blood leukocytes and molecular screening of the Calcium-sensing receptor (CASR) gene (Sanger sequencing). | Proband: a novel autosomal recessive mutation in the CaSR gene: (c.1608 + 1G > A –IVS5 + 1G > A in homozygosity). Parents: presence of the CaSR variant in heterozygosity (FHH clinical state). |
13/12/2016 | She was transferred to the NICU department of the G. Gaslini Institute of Genova (Italy). | Total calcium level stabilized around 6 mEq/L (equal to 12 mg/dl). | Increasing doses of Cinalcalcet (up to 4 mg/kg/day), low orally calcium intake (45 mg/day), intravenous fluid hyperhydration (up to 220 ml/kg/day). |
20/12/2016 | She was transferred to the Pediatric Surgery Unit of the G. Gaslini Institute of Genova (Italy). | Parathyroid glands Ultrasound: glands detectable by only the day before surgery. | Subtotal parathyroidectomy: three-excised hyperplastic parathyroid glands (5 × 3, 1.5 × 1.4 and 1.4 × 1.2 mm, respectively). |
22/12/2016 | Two days after surgery: transient asymptomatic hypocalcemia appeared (hungry bone syndrome). | X-rays of the right arm: pathological fracture of the humerus neck. | Daily Calcium gluconate replacement (0,5 ml/kg) and α-Calcidol (0,05 mcg/kg) for 40 days. |
31/01/2017 | Slow and progressive improvement of clinical conditions and hypocalcaemia. | Stop-therapy 40 days post-surgery (Calcium gluconate and α-Calcidol). | |
A longer and personalized follow up started in order to confirm if the partial parathyroidectomy was sufficient for calcium balance or a second surgical approach is needed. | |||