Jos Jansen

2 37 CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation Individual F1-II4 was last seen in 2014 at the age of two years. The most prominent finding was PMD. Hypotonia was not present. Hepatic evaluation showed elevated AST (1,089 U/l), ALT (591 U/l), ALP (1,251 U/l), and profound hepatosplenomegaly, similar to lysosomal storage disorders in the first years of life. Organ size normalized with increasing age. Individual F2-II1 (male, born in 2008) from family F2 was the only child of unrelated Italian parents. As a neonate, he suffered from prolonged neonatal jaundice and elevated AST, ALT, and hepatosplenomegaly. Low serum ceruloplasmin and hypercholesterolemia were found. On suspicion of Wilson disease (WD [MIM: 277900]), zinc treatment was started but proved unsuccessful. Genetic screening for WD failed to detect mutations in ATP7B (MIM: 606882). At the age of two years, examinations showed mild PMD and mild dysmorphic features. Biochemical analysis revealed elevated AT and ALP (AST 422 U/l, ALT 588 U/l, ALP 976 U/l), low ceruloplasmin (3.3 mg/dl), high cholesterol (381 mg/dl), and high LDL-C (332 mg/dl [normal range, 50–130 mg/dl]). Metabolic diagnostics showed a type 2 CDG pattern. A liver biopsy at the age of three years showed an increased hepatic copper concentration of 125 mg/g dry weight (normal range, < 40 mg/g dry weight; WD, > 250 mg/g dry weight). Individual F3-II2 (female, born in 1989) from family F3 was the second child of unrelated French parents. She had an uncomplicated birth but developed neonatal jaundice, which was treated successfully by phototherapy. This was accompanied by elevated AT and ALP. She was hospitalized at the age of one year due to persistent moderate hypotonia. Biochemically, she had elevated AST (1,780 U/l), ALT (390 U/l), and ALP (950 U/l, with increased bone fraction). Steatosis, fibrosis, and necrotic lesions were seen on liver biopsy. During childhood, she developed PMD with hypotonia and seizures. Biochemically, elevated AT and ALP persisted. At a later age, she developed hypercholesterolemia. CDG screening showed a type 2 pattern. During her last visit at the age of twenty-five years, she still suffered from PMD, as well as additional behavioral problems such as aggressiveness, agitation, and psychotic behavior, for which she is being treated with risperidone. Her seizures persisted despite treatment with lamotrigine. SerumAT and ALP remain elevated (AST 82 U/l, ALT 76 U/l, ALP 180 U/l) and ceruloplasmin low (10 mg/dl). Individuals F4-II1 (male, born in 2002, died in 2011) and F4-II2 (female, born in 2003) are brother and sister and were born to consanguineous Turkish