Background: Genomic assessment previously took months to result and was unable to impact clinical care in the pediatric intensive care unit (PICU). The advent of rapid exome sequencing potentially changes this. We investigated the impact of rapid exome sequencing in a pilot study on pediatric patients admitted to a single PICU with new onset metabolic/neurologic disease. Methods: Rapid exome sequencing (7 days to verbal result) was performed on (n=10) PICU patients age <6 years admitted with new onset metabolic/neurologic disease. The primary outcome of interest was inpatient LOS, which served as a proxy for inpatient cost. Results: A significant reduction in median LOS was identified when comparing PICU patients who underwent rapid exome sequencing to historical controls. From those patients who underwent rapid sequencing, 5 had likely pathogenic variants. In 3 cases with diagnostic genetic results, there was a modification to clinical care attributable to information provided by exome sequencing. Conclusions: This pilot study demonstrates that rapid exome sequencing is feasible to do in the PICU, that genetic results can be returned quickly enough to impact critical care decision-making and management. In a select population of PICU patients, this technology may contribute to a decrease in hospital length of stay.

Objective: Pyknodysostosis is a rare genetic cause of skeletal dysplasia that often goes undiagnosed even in patients with classic features. Methods: We report a case of pyknodysostosis that went undiagnosed over many years despite classic features. Results: A 21-year-old female presented to endocrinology to establish care. On evaluation she was noted to have disproportionate short stature and a past medical history notable for bilateral blindness due to optic atrophy secondary to bone enlargement and thickening of the optic nerve canal before age 7 years. She also had a history of foot fractures occurring with ambulation. Her family history was significant for consanguineous parents and relatives with similar clinical features. Physical examination revealed a short, 128-cm tall female with open anterior and mastoid fontanels, mild frontal bossing and micrognathia, evidence of double rows of teeth, and digits of varied length in both hands and feet. Plain radiographs demonstrated diffuse sclerosis and marked cortical thickening of the pelvis, femurs, metacarpals and proximal phalanges, and metatarsals as well as decreased phalangeal length and acro-osteolysis of the hands and feet. DXA demonstrated increased BMD (Z-scores +2.5 lumbar spine, +3.7 femoral neck, +4.5 total hip). Genetic testing revealed a CTSK exon 5-homozygous mutation consistent with pyknodysostosis. Conclusion: Patients with pyknodysostosis come to medical attention for a variety of reasons but often go undiagnosed even when presenting with classic features due to the rarity of the condition and the overlap with other skeletal dysplasias.

Key Clinical MessageTetraploid–diploid mosaicism in humans is exceedingly rare. We present an 11‐year‐old boy with tetraploid–diploid mosaicism and coexistent hair hypopigmentation with skin hypo‐ and hyperpigmentation. This case expands the current literature as we are not aware of previous documentation of this unique combination of pigmentary anomalies.

Management of osteoporosis in patients with alkaptonuria can be challenging. This is the first case report confirming the effectiveness of teriparatide following zoledronic acid therapy in treating osteoporosis and preventing fragility fractures in a patient with alkaptonuria.