Novel Nonsense Mutation Causes Analbuminemia in a Moroccan Family

Analbuminemia (MIM 103600) is a rare, inherited condition characterized by mild symptoms, including low blood pressure, slight edema, and fatigue (1). In the majority of cases, the disorder is detected by electrophoretic screening of plasma proteins, which shows either the complete absence of or the presence of very low amounts of circulating albumin (1) ranging from 0.01 to 1000 mg/L (2)(3). The disorder is transmitted in an autosomal recessive pattern, and to date, seven different causative mutations have been characterized by DNA sequencing within the albumin gene (4). These include three nonsense mutations (5), two splice-site mutations (6)(7), one frameshift insertion(8), and one frameshift deletion (9).We describe a novel molecular defect causing analbuminemia in a 5-year-old girl, the first child of a couple from El Jadida, Morocco. The parents were cousins, and the mother, a healthy 31-year-old primigravida, had an uncomplicated pregnancy. At birth the child was observed to be “small for gestational age” (1735 g), but otherwise unremarkable. The placenta was edematous, weighing 960 g (54% of birth weight; normal <25%). Slight peripheral edema at 2.5 weeks triggered further investigations, leading to the diagnosis of analbuminemia. Plasma albumin was “low” by protein electrophoresis, <10 g/L by a routine chemical technique, and <6 mg/L by an immunoassay using polyclonal antibodies and kinetic nephelometry. Her plasma oncotic pressure in a recumbent position was low (12 mmHg; normal, 26–31 mmHg). After albumin infusion, the edema disappeared and did not recur, despite albumin concentrations again dropping below the detection limits of the assays. Both her physical and mental development were unremarkable (10). The parents’ plasma contained decreased albumin (33 and 34 g/L, respectively) and marginally increased fractions of other proteins. Both had a low plasma oncotic pressure of 21 mmHg after 30 min in a recumbent …