Young children and adolescent children with T1DM had a low rate of partial remission. Metabolic control was poorest in young children, whereas higher dose insulin in adolescents because of insulin resistance contributes to less likelihood of having partial remission. DKA at diagnosis was associated with low rate of partial remission. It is possible that the low frequency of honeymoon phase in young children reflects more aggressive beta-cell destruction in young children.

Adrenal insufficiency may result from a wide variety of congenital or acquired disorders of hypothalamus, pituitary, or adrenal cortex. Destruction or dysfunction of the adrenal cortex is the cause of primary adrenal insufficiency, while secondary adrenal insufficiency is a result of pituitary or hypothalamic disease. Timely diagnosis and clinical management of adrenal insufficiency are critical to prevent morbidity and mortality. This review summarizes the etiologies, presentation, and diagnosis of adrenal insufficiency utilizing different dynamic hormone testing and describes current treatment recommendations and new therapies.

Vitamin D insufficiency was remarkably common in pediatric patients with primary and secondary osteopenia or osteoporosis. The inverse relationship between 25-hydroxyvitamin D and parathyroid hormone levels suggests a physiologic impact of insufficient vitamin D levels that may contribute to low bone mass or worsen the primary bone disease. We suggest that monitoring and supplementation of vitamin D should be a priority in the management of pediatric patients with osteopenia or osteoporosis.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

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Long-term glucocorticoid therapy has improved outcomes in patients with Duchenne muscular dystrophy. However, the recommended glucocorticoid dosage suppresses the hypothalamic-pituitary-adrenal axis, leading to adrenal insufficiency that may develop during severe illness, trauma or surgery, and after discontinuation of glucocorticoid therapy. The purpose of this review is to highlight the risk of adrenal insufficiency in this patient population, and provide practical recommendations for management of adrenal insufficiency, glucocorticoid withdrawal, and adrenal function testing. Strategies to increase awareness among patients, families, and health care providers are also discussed.

Hypophosphatasia (HPP) is a multi-systemic metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the mineralization-associated enzyme, tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by defective bone and dental mineralization, leading to skeletal abnormalities with complications resulting in significant morbidity and mortality. Management of HPP has been limited to supportive care until the introduction of a recently approved enzyme replacement therapy employing bone-targeted recombinant human TNSALP, asfotase alfa (AA). This new therapy has been transformative as it improves survival in severely affected infants, and overall quality of life in children and adults with HPP. This review provides an overview of HPP, focusing on important steps in the development of AA enzyme replacement therapy, including the drug design, preclinical studies in the HPP mouse model, and outcomes from clinical trials and case report publications to date, with special attention given to response to therapy of skeletal manifestations, biochemical features, and other clinical manifestations. The limitations, adverse effects, and outcomes of AA are outlined and the place in therapy for individuals with HPP is discussed.

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