LIG Audit Status

<jats:sec><jats:title>Background</jats:title><jats:p>Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the<jats:italic>OCRL</jats:italic>gene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This study is a retrospective review of clinical features reported by family based survey conducted by Lowe Syndrome Association. Frequency of non-ocular clinical feature(s) of LS and their age of onset was summarised. An LS-specific therapy effectiveness scale was used to assess the response to the administered treatment. Expression of<jats:italic>OCRL</jats:italic>and relevant neuropeptides was measured in postmortem human brain by qPCR. Gene expression in the mouse brain was determined by reanalysis of publicly available bulk and single cell RNA sequencing.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 137 individuals (1 female, 89.1% white, median age 14 years (range 0.8–56)) were included in the study. Short stature (height &lt;3rd percentile) was noted in 81% (n=111) individuals, and 15% (n=20) received growth hormone therapy. Undescended testis was reported in 47% (n=64), and median age of onset of puberty was 15 years. Additional features were dental problems (n=77, 56%), bone fractures (n=63, 46%), hypophosphataemia (n=60, 44%), developmental delay and behavioural issues.<jats:italic>OCRL</jats:italic>is expressed in human and mouse hypothalami, and in hypothalamic cell clusters expressing<jats:italic>Ghrh</jats:italic>,<jats:italic>Sst</jats:italic>,<jats:italic>Oxt</jats:italic>,<jats:italic>Pomc</jats:italic>and pituitary cells expressing<jats:italic>Gh</jats:italic>and<jats:italic>Prl</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>There is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of<jats:italic>OCRL</jats:italic>in the hypothalamus and the pituitary.</jats:p></jats:sec>