From "ACAN" to "I CAN": Restoring wellness in a boy with severe osteochondritis dissecans through diagnostic precision combined with optimal medical, surgical and rehabilitation management.

Osteochondritis dissecans (OCD) is a disease of the joints characterized by idiopathic focal subchondral lesions. Aggrecan, a proteoglycan encoded by the ACAN gene, is important for cartilage structure and function. We describe the clinical evolution of a patient with short stature, multi-focal OCD, and subchondral osteopenia that appeared linked to a novel pathogenic ACAN variant. A multi-disciplinary approach including medical (bisphosphonate) therapy, surgical intervention and rehabilitation were successful in restoring wellness and physical function.

Response to Lenvatinib in Children with Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy in children and adolescents. Infrequently, children with PTC may present with or develop disease not amenable to surgery or radioactive iodine (RAI), and systemic therapy may be an option. Lenvatinib is an oral tyrosine kinase inhibitor that is approved by the Food and Drug Administration for the treatment of adults with locally recurrent or metastatic, progressive, RAI-refractory well-differentiated thyroid carcinoma. The effect of lenvatinib in children with PTC has not been reported. PATIENT FINDINGS: Three children with metastatic PTC not amenable or refractory to RAI who responded to lenvatinib are reported. All of them developed respiratory distress requiring oxygen caused by extensive bilateral metastatic pulmonary disease. The first patient is a 14-year-old female who was initially treated with sorafenib for extensive PTC not amenable to upfront surgery or RAI. She had progressive pulmonary disease after five months, and was subsequently treated with oral lenvatinib (14 mg/m2/day). She was weaned to room air after eight weeks. The second patient is a 15-year-old male who was treated with lenvatinib (14 mg/m2/day) for iodine non-avid diffuse pulmonary disease after initial total thyroidectomy and cervical lymph node dissection. He was weaned off oxygen in six weeks. The third patient is a five-year-old male who was treated with lenvatinib (14 mg/m2/day) for pulmonary disease progression 24 months after treatment with total thyroidectomy, cervical lymph node dissection, and RAI treatment. He was weaned off oxygen one day after starting lenvatinib. Two of the patients required dose adjustments secondary to proteinuria. Otherwise, all patients tolerated lenvatinib well. The first two patients remained clinically stable on lenvatinib 23 months and 11 months after initiation of therapy, respectively, and the third patient transitioned to a tumor-specific targeted therapy after one month. SUMMARY: Three pediatric patients are reported with metastatic PTC not amenable or refractory to RAI who achieved a response on lenvatinib. CONCLUSION: Lenvatinib therapy is well tolerated and demonstrated clinical activity in children with advanced PTC. Lenvatinib should be considered in children with PTC that is refractory or not amenable to conventional management.

Evaluation of a Diabetes Coach Program Aimed to Improve the Care of Children and Youth With Type 1 Diabetes and With Compromised Control.

OBJECTIVE: To evaluate the impact of the Diabetes Coach Program (DCP) on glycated hemoglobin (A1C) levels in youth with type 1 diabetes. The youth were referred to and participated in the DCP between October 2011 and May 2016. METHODS: The Diabetes Coach visited families in their homes every 1 to 2 weeks and updated patients' diabetes teams regularly. A1C levels before the DCP were compared with A1C levels during and after discharge from the DCP. Six participating families completed satisfaction surveys via telephone. RESULTS: The DCP included 23 participants (43% male; median age, 11 years; range, 8.8 to 14.5 years); median duration of type 1 diabetes, 1.7 years (range, 0.1 to 6.3 years); median time in the DCP, 1.5 years (range, 0.2 to 2.5 years). During involvement in the program, median A1C levels decreased from baselines of 11.1% (range, 8.9% to 15.3%) to 10.2% (range, 7.6% to 12.4%) (p=0.0028). For 11 of 13 patients discharged from the DCP, the most recent median A1C levels, 11.2% (range, 9.1% to 13.6%), an average of 2.4 years later, were not different from the initial A1C levels (p=0.85). Family feedback was overwhelmingly positive. CONCLUSIONS: Participation in the DCP decreased A1C values in pediatric patients; however, the levels were not sustained after visits stopped. Pediatric health coaches may play an important role in the management of type 1 diabetes, but further research is needed to explore their benefits and how positive effects can be sustained.

A rare case of hypoglycaemia due to insulinoma in an adolescent with acutely altered mental status.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is an inherited neoplasia syndrome that generally presents with hypercalcaemia due to hyperparathyroidism. Insulin-producing tumours are less common components of the syndrome that emerge later during the course of the disease. We report here a case of an adolescent who presented with symptomatic hypoglycaemia as the first indication of MEN1. CASE: A 14-year-old boy, known to use illicit drugs, was brought to the hospital with altered mental status. He was hypoglycaemic and further investigations revealed two pancreatic insulinomas. Despite having no relevant family history, genetic evaluation showed a mutation consistent with MEN1. CONCLUSION: Insulinomas in adolescents are generally rare and even less common as a first presentation of MEN1. This diagnosis carries implications for potential future neoplasms, both benign and malignant. While intoxication is a more common case of altered mental status in adolescents, clinicians must maintain a high index of suspicion for organic disease.

Informatics of newborn screening for congenital hypothyroidism in Alberta 2005-08: flow of information from birth to treatment.

OBJECTIVES: Alberta maintains a universal screening program for congenital hypothyroidism, a condition which, when treated promptly prevents neurological impairment. Because the program relies on multiple stakeholders working in different areas, it is not known how effective the overall process is in achieving timely treatment initiation. Our objective was to analyze and describe the informatics of this program. METHODS: Data were collected from the Newborn Metabolic Screening Program and physician offices for hypothyroidism screen positive infants born between january 1, 2005 and May 31, 2008. Where data were available, times were determined for each interval: birth to sample collection, collection to receipt in central laboratory, receipt to report to the primary clinician, report to confirmatory test, and finally confirmation to thyroxin treatment. RESULTS: Complete information was found on the stages up until report generation. Although subsequent intervals had less complete data, all but 5 of the 57 newborns were followed to the endpoint of treatment initiation or diagnosis exclusion. The program was consistent and efficient in collecting, analyzing and reporting results to the primary physician by a median of 8 days (range 4-14 days). Subsequent steps resulted in a median time from birth to treatment of 11 days. There were 4 cases for which delays in clinician follow-up led to treatment initiation at 27, 34, 56 and 70 days. CONCLUSION: Newborn screening for congenital hypothyroidism in Alberta is efficient and consistent up until responsibility shifts to the community. Quality improvement work is needed to reduce potential delays.