Janet Jones

Renal Phosphate Wasting in Fibrous Dysplasia of Bone Is Part of a Generalized Renal Tubular Dysfunction Similar to That Seen in Tumor-Induced Osteomalacia

Fibrous dysplasia (FD) of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. It arises from postzygotic activating mutations of the GNAS1 gene. Hypophosphatemia due to renal phosphate wasting has been reported in association with FD as a part of the McCune‐Albright Syndrome (MAS), which is characterized by FD, skin hyperpigmentation, and precocious puberty. To date, the prevalence and mechanism of phosphate wasting has not been well studied. We evaluated 42 patients with FD/MAS. Serum and urine samples were tested for indices of mineral metabolism, amino acid handling, and markers of bone metabolism. Twenty (48%) patients had some degree of renal phosphate wasting. Nephrogenous cyclic adenosine monophosphate (cAMP) was normal in FD patients, suggesting that the underlying cause of phosphate wasting is not the presence of activating GNAS1 mutations in the kidney. In addition, there was evidence of a more generalized renal tubulopathy as represented by the presence of abnormal vitamin D metabolism, proteinuria in 36 (86%) patients, and aminoaciduria in 39 (94%) patients. Renal phosphate wasting significantly correlated with the degree of bone involvement, as assessed by serum and urine markers of bone metabolism, suggesting that a circulating factor produced by FD bone and impacting on the kidney may be the mechanism. These data show that phosphaturia as part of a generalized renal tubulopathy represents the most common extraskeletal manifestation of FD and that the observed tubulopathy is similar to that seen in tumor‐induced osteomalacia (TIO).

Latent Class Subtyping of Attention-Deficit/Hyperactivity Disorder and Comorbid Conditions

OBJECTIVE Genetic studies of attention-deficit/hyperactivity disorder (ADHD) generally use discrete DSM-IV subtypes to define diagnostic status. To improve correspondence between phenotypic variance and putative susceptibility genes, multivariate classification methods such as latent class analysis (LCA) have been proposed. The aim of this study was to perform LCA in a sample of 1,010 individuals from a nationwide recruitment of unilineal nuclear families with at least one child with ADHD and another child either affected or clearly unaffected. METHOD LCA models containing one through 10 classes were fitted to data derived from all DSM-IV symptoms for ADHD, oppositional defiant disorder, and conduct disorder (CD), as well as seven items that screen for anxiety and depression from the National Initiative for Childrens Healthcare Quality Vanderbilt Assessment Scale for Parents. RESULTS We replicated six to eight statistically significantly distinct clusters, similar to those described in other cross-cultural studies, mostly stable when comorbidities are included. For all age groups, anxiety and depression are strongly related to Inattentive and Combined types. Externalizing symptoms, especially CD, are strongly associated with the Combined type of ADHD. Oppositional defiant disorder symptoms in young children are associated with either conduct disorder or anxiety-related symptoms. CONCLUSIONS Methods such as LCA allow inclusion of information about comorbidities to be quantitatively incorporated into genetic studies. LCA also permits incorporation of milder but still impairing phenotypes than are allowed using the DSM-IV. Such methods may be essential for analyses of large multicenter datasets and relevant for future clinical classifications. This population-based ADHD classification may help resolve the contradictory results presented in molecular genetic studies.

Effects of luteinizing hormone-releasing hormone agonists on final height in luteinizing hormone-releasing hormone-dependent precocious puberty

Children with precocious puberty have accelerated skeletal maturation, which often leads to short adult height (1 -4). Long-acting luteinizing hormone-releasing hormone (LHRH) agonist treatment of LHRH-dependent precocious puberty decreases gonadotrophin and sex steroid levels and improves predicted adult height (5-33). This paper will consider the historical data on the natural history of final height in untreated children with precocious puberty, review the data on predicted height in children with precocious puberty treated with LHRH agonists, and finally review the data on the final height of children treated with LHRH agonists, including the first 44 children to reach adult height after treatment with deslorelin at the National Institutes of Health, USA.

LONG-TERM TREATMENT OF FAMILIAL MALE PRECOCIOUS PUBERTY (FMPP) WITH SPIRONOLACTONE, TESTOLACTONE, AND DESLORELIN. † 536

We have shown previously that short-term treatment with spironolactone (S), testolactone (T), and, after onset of central puberty, deslorelin (D) can normalize the rate of growth and bone maturation in boys with FMPP. To test the hypothesis that this treatment can achieve long-term normalization of the growth and development of these children, we examined the growth rate, bone maturation rate (ΔBA/ΔCA), and predicted adult height of 7 boys who were treated with S (5.7 mg/kg/day) and T (40 mg/kg/day) for at least 6 years. The mean duration of symptoms prior to treatment was 1.6 ± 0.7 years, and the mean advancement of bone age at treatment onset was 3.6± 2.8 years. D (4 mcg/kg/day) treatment was initiated at 3.0 ± 1.2 years after beginning S and T. The long-term growth results are shown in the Table: