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Contains fulltext : 137727.pdf (Publisher’s version ) (Closed access) Autosomal recessive cutis laxa (ARCL) is a connective tissue disorder characterized by wrinkled, inelastic skin, frequently associated with a neurologic involvement and multisystem disease. Next generation sequencing was performed in genetically unsolved patients with progeroid features, neurological and eye involvement to assess the underlying etiology. We describe an 6 month old child, diagnosed with a novel, homozygous nonsense mutation c.2339T>C in exon 18 of the ALDH18A1 gene, and reviewed all reported P5CS patients. So far 10 patients were described with mutations in ALDH18A1. Features of our patient that have been described in literature included cutis laxa on hands and feet, visible veins on thorax and abdomen, joint laxity, failure to thrive, short stature, microcephaly, and severe developmental and speech delay. Furthermore, abnormal fat distribution, retinal abnormalities, undescended testis, and retinitis pigmentosa have never been described in ALDH18A1. Some features described as unique in ALDH18A1 have been observed in PYCR1 patients, thus suggesting that the phenotypic overlap is higher than previously shown. In conclusion, the clinical phenotype caused by ALDH18A1 mutations is diverse, with variable degree of progeria in children, but always in association with neurologic disease. We suggest genetic testing for possible ALDH18A1 mutations in all patients with progeroid features, like wrinkled or parchment-like skin, abnormal growth, especially with central nervous system involvement and microcephaly.

Lysosomal storage diseases (LSDs) are a group of more than 40 different inherited metabolic diseases, which arise from a gene defect or mutation that impairs proper functioning of a particular lysosomal enzyme or its transport protein. Clinical presentation is very variable among the diverse group of LSDs. A defect in one lysosomal enzyme can have a greater affect on one particular tissue, for example, skeletal muscle, whereas another may have its main effect on the central nervous system. At this time there is no cure for any LSD, and in the past only symptomatic treatment was available. However, throughout the past several decades, remarkable progress has been made in developing more effective treatments such as hematopoietic stem cell transplantation (HCT) and enzyme replacement therapy (ERT). These therapies have led to significant improvement in quality of life as well as reduction in clinical symptoms for some of the LSDs. A child’s general pediatrician, often following him/her from birth, may be the first to note clinical signs and symptoms of a LSD, leading to early diagnosis and treatment. What follows is a summary of several LSD, along with an update on available and upcoming treatment modalities. ABOUT THE AUTHORS Elizabeth R. Lim-Melia, MD, is Assistant Director, Regional Medical Genetics Center, and Instructor of Pediatrics, N.Y. Medical College, Valhalla, New York. David F. Kronn, MD, is Associate Professor of Pediatrics, N.Y. Medical College. Address correspondence to: Elizabeth R. Lim-Melia, MD, 503 Grasslands Road, Valhalla, NY 10595; fax 914-345-1753; or e-mail Elizabeth_LimMelia@nymc.edu. Dr. Lim-Melia and Dr. Kronn have disclosed no relevant financial relationships. doi: 10.32800904481-20090723-09