congenital analbuminemia

Congenital analbuminemia is a metabolic condition characterized by the marked reduction or absence of human serum albumin, a key protein that helps maintain fluid balance and transport various substances in the blood. It is caused by pathogenic variants in the ALB gene and follows an autosomal recessive inheritance pattern, meaning that an affected individual inherits an abnormal copy from each parent. The condition is typically identified in childhood when signs and symptoms such as edema and fatigue become apparent. Being extremely rare, it affects fewer than 1 in one million people, and its clinical manifestations can vary considerably among those affected.

The clinical features of congenital analbuminemia result primarily from a significant deficiency of serum albumin. Nearly all affected individuals present with hypoalbuminemia, increased LDL cholesterol, fatigue, edema, elevated transferrin concentrations, osteoporosis, and hypercholesterolemia. In addition, a subset of patients may experience recurrent lower respiratory tract infections, lipodystrophy, oligohydramnios, and patent ductus arteriosus. Some children show global developmental delay, indicating cognitive and developmental challenges, though not every individual displays all of these features, and severity varies considerably.

Congenital analbuminemia is caused by mutations in the ALB gene, which disrupt the production of human serum albumin. This condition is inherited in an autosomal recessive manner, meaning that two copies of the abnormal gene—one from each parent—are required for the disease to manifest. It is more common when parents share a common ancestor, as this increases the likelihood that both carry the rare genetic variant. Genetic counseling is recommended to help families understand the inheritance pattern and implications for future pregnancies.

Currently, management of congenital analbuminemia focuses on supportive care and symptom management, as there are no foundational or approved treatments specifically indicated for this condition. Treatment is tailored to the individual and may include managing edema, monitoring cholesterol levels, and addressing developmental challenges as part of a broader multidisciplinary approach. Regular surveillance is an essential part of long-term care, helping to identify potential complications across multiple organ systems. Patients should discuss treatment options with their healthcare team to determine the most appropriate strategies, and genetic counseling is advised to assist in family planning.

The course of congenital analbuminemia varies widely among affected individuals. While many people manage the condition effectively with individualized supportive care, others may experience complications related to low albumin levels and associated metabolic imbalances. Outcomes described in medical literature continue to evolve as standards of care improve, and modern surveillance strategies help in the early detection and management of complications. Families often find it helpful to connect with specialists familiar with this condition and with genetic counselors to discuss long-term management and family planning.