Juvenile selective vitamin B₁₂ malabsorption: 50 years after its description-10 years of genetic testing

Area of Science:

• Pediatric Hematology
• Nutritional Science
• Clinical Genetics

Background:

• Juvenile selective cobalamin (Cbl) malabsorption was described 50 years ago.
• Improved living conditions have reduced nutritional and parasitic Cbl deficiency, making inherited defects more prominent.
• Cbl deficiency in children may not always present with anemia.

Purpose of the Study:

• To review the history, research, and genetic advances in understanding juvenile Cbl malabsorption.
• To highlight the diagnostic challenges posed by the unavailability of the Schilling test and the limitations of current diagnostic methods.
• To advocate for the development of improved clinical and genetic testing tools.

Main Methods:

• Literature review focusing on historical data, genetic research, and clinical case studies.
• Analysis of genetic heterogeneity and differential diagnostic complexities.
• Examination of diagnostic trends and ethnic considerations in patient populations.

Main Results:

• Inherited defects are now a primary cause of Cbl deficiency in children.
• Recent genetic research has identified numerous cases, particularly in European and North American populations with origins in the Middle East or North Africa.
• The decline of the Schilling test and the nascent stage of replacement tests lead to potential underdiagnosis.

Conclusions:

• Lack of effective clinical diagnostic tools hinders timely diagnosis of juvenile Cbl malabsorption.
• Suboptimal Cbl levels have significant, documented consequences for neurological development.
• Enhanced clinical awareness, including ethnic considerations, and rapid development of genetic testing are essential for effective management and treatment with parenteral Cbl.