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.

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.

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.

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.