Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity.

BACKGROUND: Osteosclerotic metaphyseal dysplasia (OSMD) is a unique form of osteopetrosis characterised by severe osteosclerosis localised to the bone ends. The mode of inheritance is autosomal recessive. Its genetic basis is not known. OBJECTIVE: To identify the disease gene for OSMD. METHODS AND RESULTS: By whole exome sequencing in a boy with OSMD, we identified a homozygous 7 bp deletion (c.5938_5944delGAGTGGT) in the LRRK1 gene. His skeletal phenotype recapitulated that seen in the Lrrk1-deficient mouse. The shared skeletal hallmarks included severe sclerosis in the undermodelled metaphyses and epiphyseal margins of the tubular bones, costal ends, vertebral endplates and margins of the flat bones. The deletion is predicted to result in an elongated LRRK1 protein (p.E1980Afs*66) that lacks a part of its WD40 domains. In vitro functional studies using osteoclasts from Lrrk1-deficient mice showed that the deletion was a loss of function mutation. Genetic analysis of LRRK1 in two unrelated patients with OSMD suggested that OSMD is a genetically heterogeneous condition. CONCLUSIONS: This is the first study to identify the causative gene of OSMD. Our study provides evidence that LRRK1 plays a critical role in the regulation of bone mass in humans.

Ferritin and body mass index predict cardiac dysfunction in female adolescents with anorexia of the restrictive type.

BACKGROUND AND AIM: Decreased left ventricular mass index in anorexia nervosa is amply reported. The aim of this study is to identify non-burdensome predictors of reduced left yentricular mass/height (cLVM) in a cohort of adolescent restrictive anorexic girls. METHODS: This is a retrospective study of all anorexic girls of the restrictive type referred to our tertiary eating disorder unit between September 2002 and December 2012, for somatic assessment of weig ht loss. All subjects fulfilled DMS-IV criteria, without a family history of cardiac or cardiovascular diseases. RESULTS: In all, 283 restrictive anorexic girls (age: 14.63 +/- 1.65 y; body mass index: 15.72 +/- 1.81 kg/m2) were included. Ferritin and body mass index were independent, statistically significant predictors of the corrected left ventricular mass (P <0.05). CONCLUSION: Decreased cLVM is very common in anorexia nervosa of the restrictive type. Two factors predicted decreased cLVM in our population: ferritin and BMI.

Erythema ab igne in an adolescent with anorexia nervosa.

OBJECTIVE: A rare skin lesion, erythema ab igne (EAI) is presented, in an adolescent female with anorexia nervosa. METHOD: Clinical records of this patient were compared with a pubmed search about EAI in patients with an eating disorder. RESULTS: The patient presented with localized, spider-like, erythematous and hyperpigmented skin lesions on the lower abdomen and on both thighs. Repetitive exposure to heating pads can induce reticular and macular hyperpigmentation with telangiectases without squamation. Strict avoidance of heat is advised, because there is no effective treatment. DISCUSSION: EAI is described in patients with an eating disorder. Facing an increased pain threshold, prolonged heat exposure to treat a general feeling of cold, can induce this dermatosis.

Pericardial effusions in adolescent girls with anorexia nervosa: clinical course and risk factors.

The aim of this study was to evaluate cardiac, biochemical and endocrine differences between female adolescents with anorexia nervosa (AN) with and without pericardial effusions. We studied 128 female adolescents (9.8-17.7 years) with anorexia nervosa (AN) diagnosed according to DSM-IV (American Psychiatric Association, 1994) criteria. They all underwent an echocardiographic evaluation. In 29 patients (22.2 %) a pericardial effusion (ranging between >or= 0.35-2.5 cm) was noted. None of the patients were clinically symptomatic. After 3 months of refeeding, the effusions disappeared in 18/29 patients while in 7/29 patients a pericardial effusion > 0.3 cm persisted. Risk factors for development of effusions were a BMI or= 25% and IGF-1-level

Intermittent Brugada syndrome in an anorexic adolescent girl.

We report an anorexic adolescent girl with an intermittent Brugada syndrome. A 14-year-old anorexic girl with a body mass index (BMI) of 13.15 kg/m2 was admitted in the acute state of the disease with an ST elevation in V1 and V2, suggestive of Brugada syndrome. After 1 month of re-feeding, a control electrograph (ECG) was normal, but after an 8-month follow-up control with a nearly normal BMI, the ECG was again suggestive of Brugada syndrome. A genetic analysis of the gene SNC5A established a genetic change (p Leu 1582 pro), which provides the final explanation for the Brugada syndrome. Every rhythm problem in the acute state or during the re-feeding procedure deserves a strict follow-up to distinguish iatrogenic from heritable rhythm problems. .