Decoding the Mystery: Understanding, Diagnosing, and Using Genetic Testing for Methylmalonic Acidemia with Homocystinuria cblC

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Understanding Methylmalonic Acidemia with Homocystinuria cblC

Methylmalonic acidemia with homocystinuria cblC is a rare genetic disorder characterized by the body’s inability to properly process certain proteins and fats. This results in the accumulation of toxic substances, such as methylmalonic acid and homocysteine, which can cause a range of health problems, including developmental delays, neurological issues, and eye abnormalities. The severity of the disorder varies widely, with some individuals experiencing mild symptoms and others suffering from life-threatening complications.

Ocular Manifestations of the Disease

According to a study published in Ophthalmic Genetics, patients with cobalamin C (cblC) and cobalamin A (cblA) types of methylmalonic acidemia can experience a wide range of ocular manifestations. These can range from mild optic nerve atrophy to severe macular or retinal degeneration. Early detection and treatment of these eye problems are crucial to preserving vision and improving the quality of life for affected individuals.

Diagnosing Methylmalonic Acidemia with Homocystinuria cblC

Diagnosing this disorder can be challenging due to its rarity and the variability of its symptoms. However, newborn screening programs have proven to be effective in identifying the disease early in life. A study published in Frontiers in Genetics found a high overall incidence of inborn errors of metabolism, including methylmalonic acidemia with homocystinuria cblC, in a Chinese population. The study identified mutations in the PAH, SLC22A5, and MMACHC genes as the leading causes of these metabolic disorders.

Genetic Testing for Methylmalonic Acidemia with Homocystinuria cblC

Genetic testing plays a crucial role in diagnosing and managing methylmalonic acidemia with homocystinuria cblC. A study published in Clinical Laboratory conducted clinical and molecular genetic analysis of a family with cblC disease, identifying compound heterozygous mutation in the MMACHC gene. These findings can help clinicians make a definitive diagnosis and guide treatment strategies for affected individuals.

Carrier Screening for Methylmalonic Acidemia with Homocystinuria cblC

Carrier screening is another important application of genetic testing for this disorder. A study published in Intractable & Rare Diseases Research established a PCR technique involving high-resolution melting (HRM) for large-scale hotspot mutation screening of MMACHC carriers in Shandong Province, China. The study found a high carrying rate of MMACHC mutations in the local population, highlighting the importance of carrier screening in regions with a high prevalence of the disorder.

Prenatal and Preimplantation Genetic Testing for Methylmalonic Acidemia with Homocystinuria cblC

Genetic testing can also be used to identify the disorder in unborn babies and embryos during in vitro fertilization (IVF) procedures. Prenatal testing can help families make informed decisions about the management of an affected pregnancy, while preimplantation genetic testing can help couples undergoing IVF select embryos without the MMACHC mutation, reducing the risk of having a child with the disorder.

Conclusion

Methylmalonic acidemia with homocystinuria cblC is a complex and challenging disorder, but advances in genetic testing have improved our ability to diagnose, manage, and even prevent the disease. By understanding the genetic basis of the disorder and utilizing cutting-edge testing techniques, clinicians can better support affected individuals and their families, ultimately improving outcomes and quality of life for those living with this rare condition.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)