Objectives Hereditary hypophosphatemic rickets (HR) is conventionally treated with phosphate and calcitriol. Exploring genotype and phenotypic spectrum of X-linked hypophosphatemic rickets (XLHR), focusing on short-term, long-term, and pubertal impact of conventional treatment was aimed. Methods Sixteen patients from 12 unrelated families with HR were analyzed for phosphate regulating endopeptidase homolog X-linked (PHEX) mutation. Initially Sanger sequencing analysis was performed. If PHEX mutation was not detected, multiplex ligation-dependent probe amplification (MLPA) was performed. If molecular defect was detected, first-degree relatives were analyzed. Thirteen patients (81%) and five first-degree relatives with XLHR were evaluated for genotype–phenotype or gender-phenotype correlation. Clinical characteristics and response to conventional treatment were determined retrospectively. Results Nine different PHEX mutations were identified; four splice-site, three point mutations, and two single exon deletions. Four were novel mutations. Despite conventional treatment, median adult height was lower than median height on admission (−3.8 and −2.3 SDS, respectively), metabolic and radiographic recovery were not achieved, adherence was low (30%). Although mean adult height was better in compliant patients than noncompliants (−2.6 vs. −3.7 SDS, respectively), they were still short. Correlation between phenotype and genotype or gender could not be shown. Median phosphate decreased significantly throughout puberty (p=0.014). Median pubertal height was lower than prepubertal height (−4.4 vs. −3.6 SDS; respectively), pubertal growth spurt was not observed. Among five patients with a follow-up longer than five years, three had nephrocalcinosis (60%), two had hyperparathyroidism (40%), 4/6 (33%) required correction osteotomy. Conclusions Conventional treatment appears to have limited effect on metabolic, clinical and radiographic recovery in XLHR. Metabolic control and growth worsened during puberty. Although, long-term adverse effects are yet to be seen, introduction of burosumab as first-line treatment may be an alternative after infancy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) (polyglandular endocrinopathy type 1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). The major clinical features of APECED are hypoparathyroidism, adrenal insufficiency (Addison disease), and chronic mucocutaneous candidiasis. This disease is also associated with multiple other and uncommon autoimmune (autoimmune hepatitis, autoimmune enteropathy, atrophic gastritis with or without pernicious anemia, gonadal failure, diabetes mellitus, hypothyroidism, functional hyposplenism), ectodermal (alopecia and vitiligo), and inflammatory (intestinal lung disease, nephritis) features. Here, we report a case of a 13-year-old Turkish boy who presented wih enteropathy and lung abscess. Molecular genetic analysis demonstrated a homozygous frameshift mutation (p.Asp70fs, c.208_209insCAGG) in exon 2, in AIRE gene. APECED may present with severe, life-threatening infections due to functional hyposplenism. Multidisciplinary approach, careful follow-up, and molecular genetic studies are needed.

Objectives Neonatal-onset organic acidemias (OAs) account for 80% of neonatal intensive care unit (NICU) admissions due to inborn errors of metabolism. The aim of this study is to analyze clinical features and follow-up of neonates diagnosed with OAs in a metabolic referral center, focusing on perinatal characteristics and the impact of first the metabolic crisis on long-term outcome. Methods Perinatal features, clinical and laboratory characteristics on admission and follow-up of 108 neonates diagnosed with OAs were retrospectively analyzed. Global developmental delay, abnormal electroencephalogram (EEG) or brain magnetic resonance imaging (MRI), chronic complications, and overall mortality. Associations between clinical findings on admission and outcome measures were evaluated. Results Most prevalent OA was maple syrup urine disease (MSUD) (34.3%). Neonates with methylmalonic acidemia (MMA) had significantly lower birth weight (p<0.001). Metabolic acidosis with increased anion gap was more frequent in MMA and propionic acidemia (PA) (p=0.003). 89.1% of OAs were admitted for recurrent metabolic crisis. 46% had chronic non-neurologic complications; 19.3% of MMA had chronic kidney disease. Abnormal findings were present in 26/34 of EEG, 19/29 of MRI studies, and 32/33 of developmental screening tests. Metabolic acidosis on admission was associated with increased incidence of abnormal EEG (p=0.005) and overall mortality (p<0.001). Severe hyperammonemia in MMA was associated with overall mortality (33.3%) (p=0.047). Patients diagnosed between 2007–2017 had lower overall mortality compared to earlier years (p<0.001). Conclusions Metabolic acidosis and hyperammonemia are emerging predictors of poor outcome and mortality. Based on a large number of infants from a single center, survival in neonatal-onset OA has increased over the course of 30 years, but long-term complications and neurodevelopmental results remain similar. While prompt onset of more effective treatment may improve survival, newer treatment modalities are urgently needed for prevention and treatment of chronic complications.

A genetic defect of 11 β-hydroxysteroid dehydrogenase causes apparent mineralocorticoid excess syndrome. Since 50 days of life, our patient was hospitalized several times for various reasons including hypokalemia. At the age of 3.3 years, she was diagnosed with severe hypertension (160/120 mmHg). She also had left ventricular hypertrophy and hypertensive retinopathy and referred to our center. Her renal function and electrolytes were normal except for hypokalemia. She was on captopril treatment; nifedipine and propranolol were added. Plasma renin and aldosterone concentrations were 1.13 pg/ml (1–8.2 pg/ml) and 12.2 ng/dl (35–300 ng/dl), respectively. Severe hypertension, hypokalemia, low renin and aldosterone levels pointed to the diagnosis of apparent mineralocorticoid excess syndrome. Strict salt-restricted diet and potassium citrate were ordered. Genetic analysis of the HSD11B2 gene showed c.623G>A (p.Arg208His). Spironolactone was initiated. On follow-up, amiloride was added and her blood pressure was controlled. In patients with severe HSD11B2 mutation, combination therapy of spironolactone with amiloride could be effective in controlling blood pressure.

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