[Two cases of symptomatic West syndrome suffering from severe respiratory syncytial virus-induced bronchiolitis].

We report two cases of symptomatic West syndrome with severe respiratory syncytial virus (RSV)-induced bronchiolitis: one was a 9-month-old boy who was hospitalized for shock, and the other was a 15-month-old boy in pre-shock condition. Both cases needed mechanical ventilation for approximately 2 weeks. Seizures from the primary disease worsened in both patients during the infection, and both needed long periods of hospitalization, which resulted in a considerable reduction in their quality of life and that of their families. According to a one-year epidemiological survey of RSV infection conducted in 2004-2005 in Nagano prefecture, 7 of 238 hospitalized RSV cases were found to have basic neuromuscular disorders. Compared to patients with chronic lung disease or other primary diseases, they were older, had higher incidence of mechanical ventilation, and required longer hospitalization. Neuromuscular disorders may thus be an important risk factor for severe forms of RSV infection. Although children with such disorders should be protected from RSV, they are currently excluded from the indication for palivizumab administration as passive immunization against RSV in Japan.

Novel compound heterozygous mutation of the MC2R gene in a patient with familial glucocorticoid deficiency.

Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterised by glucocorticoid insufficiency without mineralocorticoid deficiency. Here, we report a 2 year-old girl with FGD, showing tall stature and skin pigmentation, but no abnormalities of the external genitalia. Serum sodium, potassium and chloride levels were within normal ranges. Endocrinological analysis revealed low serum cortisol (<5.5 nmol/1), elevated plasma ACTH (875.2 pmol/1) and low 17alpha-hydroxyprogesterone (< 0.303 nmol/l). We suspected the patient of having FGD type 1. Direct and allele-specific sequence analyses of the melanocortin 2 receptor gene (MC2R) revealed compound heterozygous mutations (C21Y and R146H) in the MC2R gene. Her father and mother each had heterozygous C21Y and R146H mutations, respectively, without symptoms of glucocorticoid deficiency. This is the first report of FGD associated with a compound heterozygous mutation of C21Y and R146H in the MC2R gene.

Effect of parathyroid hormone administration in a patient with severe hypoparathyroidism caused by gain-of-function mutation of calcium-sensing receptor.

Hypoparathyroidism caused by gain-of-function mutations of the calcium-sensing receptor (CaR) in the transmembrane domain is usually severe and difficult to manage. A patient with severe hypoparathyroidism, caused by CaR activating mutation F821L, was treated for 3 days (Day 1 to Day 3) with synthetic human parathyroid hormone 1-34 (teriparatide, PTH). An Ellsworth-Howard test of the patient revealed normal responses of urine phosphate and cyclic AMP excretion, indicating that the patient's renal tubules normally responded to extrinsic PTH. On Day 1 to Day 3, 0.9 microg/kg/day of PTH was administered subcutaneously twice daily at 0800 and 2000. On Day 1, the serum calcium level that was 1.8 mmol/l before PTH administration increased to 2.1 mmol/l at 1200, and gradually decreased to 1.8 mmol/l at 2000. On Days 2 and 3, the maximum calcium levels were 2.5 and 2.4 mmol/l, respectively, at 1200. At 2000, they returned to or below basal levels at 0800. On Day 4 without PTH administration, the calcium levels were maintained at the basal levels at Day 0. The urine calcium/creatinine (Ca/Cr) ratio that was high (>0.4) before PTH injection decreased after PTH administration (0.4>). Changes in the ionized calcium levels were almost parallel with the total calcium levels. The serum inorganic phosphate (IP) level decreased to 2.4 mmol/l at 1000, but gradually increased before the second PTH injection to the level at 0800 on Day 1. The minimum IP level on Days 2 and 3 was 2.1 mmol/l and 2.0 mmol/l, respectively. In contrast to the remarkable changes in the serum calcium level by PTH treatment, the serum magnesium levels showed few changes. These results indicate that PTH therapy could be effective in correcting serum and urine calcium and the phosphate levels in hypoparathyroidism caused by activating mutation of CaR.