Jos Jansen

94 Chapter 4 Eleven patients from six families with ATP6AP1 deficiency were diagnosed within their first year of life. They share a liver phenotype that is compatible with TMEM199- and CCDC115 deficiency. Findings on liver biopsies varied from normal liver histology to severe cirrhosis. Hepatosplenomegaly was present in patients from most families. ATP6AP1 deficiency is defined by the combination of liver injury and immunodeficiency. Almost all patients had a phenotype of recurrent bacterial infections with hypogammaglobulinemia and leukopenia. Table 3. Extra-hepatic symptoms of V-ATPase assembly factor deficiencies Extra-hepatic symptoms TMEM199-CDG CCDC115-CDG ATP6AP1-CDG Dysmorphic facial features - + - Psychomotor disability +/- + +/- Neurological symptoms - Hypotonia +/- + +/- - Seizures - - +/- - Sensineural hearing loss - - + Hematologic symptoms - abnormal coagulation factors +/- +/- n.a. - anemia n.a. +/- n.a. - leukopenia n.a. n.a. + - hypogammaglobulinemia - - + Creatine Kinase n.a. n.a. Splenomegaly - + + Hypoglycemia n.a. +/- n.a. Hypercholesterolemia + + n.a. Bone anomalies - - - Treatment As with most CDG, treatment of V-ATPase assembly factor deficiencies is empirical. Treatment of TMEM199 deficiency was not indicated for three out of four patients as AST, ALT, and AP regressed to normal. A fourth patient received antiepileptics for recurrent seizures. Zinc treatment was tried in a patient with CCDC115 deficiency without avail. ATP6AP1 deficient patients develop hypogammaglobulinemia, successfully treated by IV immunoglobulines. Liver