Simultaneous kidney and pancreas transplantation in a patient with nail-patella syndrome and insulin-dependent diabetes.

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal dominant disorder caused by a mutation in LIM-homeodomain transcription factor 1-beta (LMX1B) and characterized by nail dystrophy, skeletal changes, glaucoma, and kidney disease with up to 30% of patients progressing to kidney failure. Autoimmune diseases, including thyroid disease, have been reported previously in patients with NPS. CASE-DIAGNOSIS/TREATMENT: We report the case of a pediatric patient with NPS with kidney failure, hypothyroidism, and type 1 diabetes mellitus. The patient's pedigree and identification of a kidney specific mutation in LMX1B was a result of whole exome sequencing. Clinical data was obtained from retrospective chart review and included the 1-year post-transplant follow-up period. At 15 years of age, our patient received a simultaneous kidney-pancreas transplantation, from a 3 HLA antigen mismatched deceased donor. The donor was CMV + , EBV - and our patient was CMV - , EBV - at time of transplant. Our patient maintained normal kidney function and euglycemia without insulin therapy at 1 year post-transplant. CONCLUSIONS: The patient's hypothyroidism, diabetes mellitus, and kidney failure may all be related to LMX1B mutation. Further study is needed to clarify the genetic link between these processes. Simultaneous kidney-pancreas transplantation can be used to successfully treat diabetes mellitus and kidney failure in a pediatric patient.

Recurrent Concurrent Diabetic Ketoacidosis and Thyroid Storm.

Diabetic ketoacidosis (DKA) and thyroid storm are serious complications of underlying disease states. Either condition can induce the other, and the co-occurrence of these conditions is uncommon. We present the case of an adolescent patient with type 1 diabetes and autoimmune hypothyroidism who developed recurrent concurrent DKA and thyroid storm twice in an eight-month period. The simultaneous development of DKA and thyroid storm is uncommon with only 28 cases previously reported. Co-presentation of these two life-threatening conditions occurs in people with either preexisting diabetes, thyroid disease, or both. The purported pathophysiology of how DKA and thyroid storm affect the other is discussed.

Rare PHEX variant with insidious presentation leads to a delayed diagnosis of X-linked hypophosphatemia.

A 7-year-old girl without a significant previous medical history was diagnosed with X-linked hypophosphatemic rickets (XLHR) due to a rare, most likely pathogenic, PHEX gene variant after a 4-year delayed diagnosis due to mild clinical presentation. At 2 years of age, her intoeing and femoral bowing were attributed to physiologic bowing and borderline vitamin D sufficiency, despite phosphorus not being measured. Hypophosphatemia was eventually detected after incomplete improvement of bowing and leg length discrepancy with suboptimal linear growth. This rare PHEX variant (c.1949T>C, p.Leu650Pro) further supported the clinical diagnosis of XLHR. Treatment with burosumab (an anti-FGF23 monoclonal antibody) normalised phosphorus and alkaline phosphatase levels and improved her bowing. The diverse phenotypic presentation of this variant can result in delayed diagnosis and highlights the importance of prompt assessment of phosphorus levels in patients with skeletal deformities to ensure timely recognition and treatment.

Pathogenicity of a glucokinase gene mutation and description of its clinical phenotype.

Glucokinase gene (GCK) mutations comprise approximately 10% of cases of maturity-onset diabetes of the young (MODY). Over 800 different mutations in GCK have been reported in the Human Gene Mutation Database, the vast majority of which result in MODY type 2. The missense mutation p.Leu122Val is listed in that database as "disease-causing;" however, the National Center for Biotechnology Information ClinVar database (Variation ID 585919) reports that this mutation is of "uncertain significance." Both databases reference the same Italian pediatric patient reported by Massa et al in 2001, but no phenotypic description of the patient is included in the original article. We report a pedigree of three patients over two generations affected with GCK mutation c.364C > G (p.Leu122Val) to support the clinical significance of this mutation and to provide the first phenotypic description of patients with this particular mutation.

Severe Hypertriglyceridemia With New-Onset Type 1 Diabetes in Diabetic Ketoacidosis.

Hypertriglyceridemia is a complication in the presentation of diabetic ketoacidosis (DKA) but has been reported in the pediatric population infrequently. We report a 13-year-old female with new onset type 1 diabetes in DKA, who developed extreme hypertriglyceridemia. Our patient's case is unique as her triglyceride levels were markedly higher than those in other reports and required a longer duration of time to resolve. We review the literature on the concomitant presentation of DKA and hypertriglyceridemia, as well as its pathophysiology and treatment.

Sinusitis, an under-reported adverse effect in children treated with radioactive iodine therapy and review of the current literature.

Background Radioactive iodine (RAI) therapy is prevalent in the treatment of Graves' disease. Adverse effects in pediatrics are not well-described. Case presentation A 13-year-old female underwent RAI therapy for Graves' disease. Eight days later, she developed facial pain and forehead burning. She was diagnosed with sinusitis and started on pseudoephedrine with resolution in 24 h. Conclusions She endured prolonged discomfort due to an under-recognized adverse effect of RAI. Studies identify the nose as a site of RAI accumulation and smaller nasal passages may predispose children to sinusitis. We report the first pediatric case of sinusitis following RAI. With the increasing use of RAI to treat Graves' disease, clinicians must recognize this adverse effect.

Pediatric stroke as the presenting symptom of new-onset type 1 diabetes mellitus without DKA: case report and literature review.

Background Stroke and other neurologic complications are rare in pediatric type 1 diabetes mellitus (T1DM) without severe diabetic ketoacidosis (DKA) or poor glycemic control. Case presentation A previously healthy, 10-year-old female presented with acute thalamic stroke, non-acidotic new T1DM diagnosis and negative hypercoagulopathy workup. She received routine insulin therapy and aspirin, and returned to neurologic baseline within a year without stroke recurrence. Conclusions The contribution of non-acidotic hyperglycemia to stroke risk is better described in adults. Even though unable to prove causality, this case should at least raise awareness of the possible association of pediatric new-onset diabetes and stroke for optimal outcomes.

Hypogonadotropic hypogonadism in a female patient with congenital arhinia.

The association of anosmia and congenital hypogonadotropic hypogonadism (CHH) is well described; however, congenital arhinia is a malformation associated with CHH that occurs much more rarely. There have been three reports of male patients with hypogonadism and congenital arhinia in the literature to date. We present the first case of arhinia associated with CHH in a female patient. A 14 years and 8 months female with congenital arhinia presented with delayed puberty. Physical examination and laboratory evaluation were consistent with hypogonadotropic hypogonadism. She had no other hormone deficiencies and brain magnetic resonance imaging demonstrated a normal pituitary gland. Abdominal ultrasound showed a prepubertal uterus and ovaries. She was subsequently started on sex steroid treatment to induce secondary sexual characteristics. This case demonstrates that abnormalities of nasal development may provide an early diagnostic clue to hypogonadotropic hypogonadism, particularly in female patients who would not manifest classic signs of CHH in infancy (micropenis and cryptorchidism). Early diagnosis of CHH and timely initiation of sex steroid therapy is important to prevent comorbidities related to pubertal delay.

Etiological and clinical characteristics of central diabetes insipidus in children: a single center experience.

BACKGROUND: Central diabetes insipidus (CDI) results from a number of conditions affecting the hypothalamic-neurohypophyseal system to cause vasopressin deficiency. Diagnosis of CDI is challenging, and clinical data and guidelines for management are lacking. We aim to characterize clinical and radiological characteristics of a cohort of pediatric patients with CDI. METHODS: A chart review of 35 patients with CDI followed at North Carolina Children's Hospital from 2000 to 2015 was undertaken. The frequencies of specific etiologies of CDI and characteristic magnetic resonance imaging (MRI) findings were determined. The presence of additional hormone deficiencies at diagnosis and later in the disease course was ascertained. Patient characteristics and management strategies were evaluated. RESULTS: The cohort included 14 female and 21 male patients with a median age of 4.7 years (range, less than 1 month to 16 years) at diagnosis. Median duration of follow-up was 5 years (range, 2 months to 16 years). The cause of CDI was intracranial mass in 13 patients (37.2 %), septo-optic dysplasia in 9 patients (25.7 %), holoprosencephaly in 5 patients (14.2 %), Langerhans cell histiocytosis in 3 patients (8.6 %), isolated pituitary hypoplasia in 2 patients (5.7 %), and encephalocele in 1 patient (2.9 %). Patients were symptomatic for a mean of 6.3 months (range, less than 1 month to 36 months) prior to diagnosis of CDI. Growth hormone (GH), thyrotropin (TSH), adrenocorticotropic hormone (ACTH), and gonadotropin deficiencies were present at diagnosis in 34, 23, 23, and 6 % of patients, respectively. GH, TSH, ACTH, and gonadotropin deficiencies were diagnosed during follow-up in 23, 40, 37, and 14 % of patients, respectively. In patients with structural CNS abnormalities, development of additional hormone deficiencies occurred anywhere from 2 months to 13 years after the time of initial presentation. CONCLUSIONS: All patients in our cohort had an underlying organic etiology for CDI, with intracranial masses and CNS malformations being most common. Therefore, MRI of the brain is indicated in all pediatric patients with CDI. Other pituitary hormone deficiencies should be investigated at diagnosis as well as during follow-up.

Slipped capital femoral epiphysis and associated hypothyroidism. A review of the literature with two classic case examples.

Slipped capital femoral epiphysis (SCFE) is a relatively common hip disorder often seen in overweight, peripubertal children. Although the exact etiology is uncertain, it is generally accepted that underlying endocrinopathies play a role in the pathogenesis. Hypothyroidism is the endocrine disorder cited most commonly in association with SCFE, and patients often have no history of thyroid dysfunction at the time of presentation. Despite being a well-recognized risk factor, recommendations for screening thyroid function in patients with typical presentations of SCFE have not been deemed cost-effective; however, there is data to support screening for hypothyroidism in patients with atypical presentations of SCFE or short stature. Hypothyroidism may have a significant impact on healing and bone union after surgical management of SCFE and there is a paucity of case reports in the literature describing potential peri- and postoperative complications. We performed a systematic review of the literature of all reported cases of SCFE with associated hypothyroidism using the search terms, which demonstrated a physiologic relationship between hypothyroidism and SCFE. Two case reports of SCFE in patients with hypothyroidism and associated complications are presented with the literature review. There is a physiologic relationship between thyroid dysfunction and SCFE, and we postulate that profound hypothyroidism may contribute to delayed healing or nonunion in patients undergoing operative management. We support the recommendation to screen patients with short stature, atypical presentation of SCFE, or perisistent nonunion after surgery. In cases of hypothyroidism, we recommend thyroid hormone replacement and laboratory confirmation of return to euthyroid state prior to operative intervention.