Neonatal severe hyperparathyroidism secondary to a novel homozygous CASR gene mutation.

Neonatal severe hyperparathyroidism (NSHPT) is a rare autosomal recessive disease. Children present within the first 6 months of life and more commonly in the first few weeks. Common presentation is poor feeding, polyuria, dehydration, lethargy, failure to thrive, hypotonia, gastrointestinal dysmotility, osteopenia and symptoms of respiratory distress due to a poorly developed chest cage. We present a case of a 2-month old girl with severe hypercalcemia and hyperparathyroidism. She was found to have a novel homozygous mutation in the acceptor splicing site of intron 4 (c.1378 -2A>G) of the calcium sensing receptor gene (CASR). This mutation causes frame shift deletion of exon 5 and insensitivity of CASR to calcium. The patient was treated with intravenous fluids, fruosemide, calcitonin, intravenous pamidronate and oral cinacalcet. She did not respond to medical treatment. Parathyroid gland imaging including ultrasound, MRI and sestamibi nuclear scan were not helpful in localizing the glands. Her symptoms resolved following total parathyroidectomy. She is being treated with alfacalcidiol and calcium supplements to maintain normal serum calcium and phosphate. She achieved her normal developmental milestones.

Identification of cystic fibrosis transmembrane conductance regulator gene (CFTR) variants: A retrospective study on the western and southern regions of Saudi Arabia.

OBJECTIVES: To investigate the geographic distribution of common cystic fibrosis (CF) variants in the western and southern regions of Saudi Arabia. METHODS: A retrospective study was conducted on 69 patients diagnosed with CF at King Faisal Specialist Hospital & Research Center, Jeddah. Patient data were collected retrospectively between June 2000 and November 2021. Various parameters were considered, including patient demographic information, CFTR variants, and respiratory cultures. RESULTS: We identified 26 CFTR variants in 69 patients with CF, including one novel variant that had not been reported or published before (1549del G) in 2 patients with CF. The 6 most prevalentvariants were as follows: c.1521_1523delCTT (19%), c.1418delG (10.2%), c.579+1G>T (8.8%), c.2988+1G>A (8.8%), c.3419 T>A (7.2%), and c.4124A>C (5.8%). In addition, respiratory cultures revealed that Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae were highly common among patients with CF. CONCLUSION: This study highlighted features of patients with CF residing in the Western and Southern regions of Saudi Arabia. Six of the 26 CFTR variants were common in these patients. We also report, for the first time, a novel variant and other CFTR variants that are yet to be reported in Saudi Arabia. These findings could help establish a foundation for cystic fibrosis screening in Saudi Arabia and may assist in clinical diagnosis and prognosis.

Outcome of COVID19 in Patients With Osteogenesis Imperfecta: A Retrospective Multicenter Study in Saudi Arabia.

Background: Although genetic diseases are rare, children with such conditions who get infected with COVID-19 tend to have a severe illness requiring hospitalization. Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen resulting in fractures and skeletal deformities. Kyphoscoliosis, restrictive lung disease, and pneumonia worsen the prognosis of patients with OI. The use of bisphosphonate improves bone mineral density (BMD) and reduces fractures in OI. There is no literature describing the impact of COVID-19 in patients with OI. Methodology: A retrospective multi-center study was performed in three hospitals in Jeddah and Riyadh, Saudi Arabia, from March 1st, 2020, until August 31st, 2021, aiming to evaluate the outcome of COVID-19 in patients with OI. Demographics, vaccination status, underlying kyphoscoliosis, functional status, use of bisphosphonate, BMD, and COVID-19 severity, and course were recorded for all patients. Results: Twelve cases of confirmed COVID-19 were identified among 146 patients with OI. 9 (75%) of patients were less than 18 years, 6 (50%) were male, 5 (41%) had kyphoscoliosis, and 5 (41%) were wheelchair-bound. 6 (50%) received bisphosphonate, and 7(58%) had normal BMD. All patients had mild disease and did not require hospitalization. None of OI the patients with COVID-19 were fully vaccinated before the infection, and some were ineligible for vaccination. Conclusion: Patients with OI and COVID-19 in our study recovered without complications, unlike patients with other genetic diseases. Young age and mild illness contributed to the favorable outcome. Half of the patients received bisphosphonate and had normal BMD.