Abstract: SUN 028
Idiopathic Hypoparathyroidism in Neurofibromatosis Type 1-Noonan Syndrome: A Case Report
Background: Hypoparathyroidism is a rare endocrine disorder in childhood. Most cases are related to genetic syndromes, others to autoimmune polyglandular syndrome and a small subset is idiopathic. We present a novel case of hypoparathyroidism in an adolescent with an association of Neurofibromatosis type 1 and Noonan syndrome (NFNS).view more
Background: Hypoparathyroidism is a rare endocrine disorder in childhood. Most cases are related to genetic syndromes, others to autoimmune polyglandular syndrome and a small subset is idiopathic. We present a novel case of hypoparathyroidism in an adolescent with an association of Neurofibromatosis type 1 and Noonan syndrome (NFNS).
Case description: A 15-year-7-month old male hospitalized with pancytopenia was diagnosed with acute lymphocytic leukemia. He had prior history of mild developmental delay, short stature treated with growth hormone and lensectomy for juvenile cataracts. Upon admission he had hypocalcemia (3.8 mg/dL, n:>8.6) and hyperphosphatemia (9.2 mg/dL, n:<5.8) with normal albumin (4 gm/dL, n:3.6-5.1) and potassium (3.8 mmol/L, n:3.5-5.2). He had no past history of hypocalcemia. Normal uric acid (3.1 mg/dL, n:3-8) ruled out tumor lysis syndrome. Hypoparathyroidism was diagnosed based on a concomitant low PTH level (3.7 pg/mL, n:>10). Correction of hypocalcemia required calcium and calcitriol. He briefly needed a phosphate binder for hyperphosphatemia. Renal ultrasound was normal.
The patient had café au lait spots, axillary and inguinal freckling, Lisch nodules, scoliosis and was Tanner V for testicular size. He also had clinical features of Noonan syndrome(NS) with webbed neck, hypertelorism, low set ears, pectus excavatum, wide spaced nipples and short stature. His biological father and brother had Neurofibromatosis type 1(NF1) phenotype. Genetic testing revealed a pathogenic NF-1 gene mutation but negative NS gene panel.
His clinical course was complicated with a four month period of hypercalcemic episodes, during which all calcium supplementation was withdrawn. The PTH levels remained low(<3.4 pg/mL) with hypercalcemia (11.8 mg/dL) and normal phosphorus(4.1 mg/dL). He was euthyroid, adrenally sufficient and had no hypervitaminosis. Hypercalcemia was attributed to chronic immobilization. After these episodes of hypercalcemia, he became hypocalcemic again (5.2 mg/dL) with hyperphosphatemia (5.4 mg/dL) and low PTH level (<3.4 pg/mL), needing ongoing calcium supplementation and calcitriol.
Conclusion: NF1 and the NS disorders are caused by mutations in the same RAS-MAPK2 developmental pathway. Some individuals with proven NF-1 mutations have NS like appearance but no genetic mutation. This variant of NF1 phenotype is called NFNS, which is our patient’s diagnosis. Juvenile cataracts in him may have been related to chronic hypocalcemia, explaining his lack of symptoms despite severe hypocalcemia at presentation. There are only two case reports of hypoparathyroidism with NS1,2 but none with NF1. The only reported pediatric case of NS and hypoparathyroidism also had DiGeorge, and the hypoparathyroidisim was attributed to the latter. To the best of our knowledge this is the first case report of hypoparathyroidism in a patient with NFNS.