Newborn screening was able to successfully detect mitochondrial carnitine-acylcarnitine disorders including long chain fatty acid oxidation disorder (LCFAOD), as published in Frontiers in Genetics.
This prospective and single-center study led by Zhou included 4,070,374 newborns from January 2009 to June 2021 from Children’s Hospital Zhejiang University School of Medicine in China. The researchers discovered a total incidence of 1 in 203,518 live births with mitochondrial carnitine-acylcarnitine cycle disorders, a form of LCFAOD.
Among those, carnitine palmitoyltransferase 1 (CPT1) deficiency was the most prevalent with an incidence of 1 in 339,197, followed by carnitine palmitoyltransferase 2 (CPT2) deficiency and carnitine-acylcarnitine translocase deficiency (CACTD) with an equal incidence of 1 in 1,017,593.
All participants had dried blood samples randomly collected from the third up to the seventh day of life to assess levels of free carnitine (C0), acetylcarnitine, propionylcarnitine, butyrylcarnitine, lauroylcarnitine (C12), myristoylcarnitine, palmitoylcarnitine (C16), palmitoylcarnitine (C16:1), octadecanoylcarnitine (C18), and oleylcarnitine (C18:1). Patients with high C0 or C0/(C16+C18) ratio were preliminarily diagnosed with CPT1, while suspecting CPT2 or CACTD in patients with either decreased C0 levels or C0/(C16+C18) ratio, or elevated C12-C18:1 levels.
Read more about LCFAOD diagnosis
All patients that possibly had an LCFAOD further underwent genetic testing, revealing 20 confirmed cases of such disorders. For CPT1, out of the 12 cases, 11 had elevated C0 levels and C0/(C16+C18) ratio. Most of these newborns were asymptomatic, and 14 different mutations could be identified, including 11 novel variants.
All patients confirmed for CPT2 displayed elevated values in all long-chain acylcarnitine levels except 1 case of CPT2 with normal C12. Of these, 2 (50%) were asymptomatic, 2 died, and 75% of the mutations were new. Similarly, only 1 case of CACTD had normal C12, C18, and C18:1 values, and while all 4 had a disease onset after birth, 3 (75%) died. All of the patients’ genotypes have been previously reported for this disease.
Although rare, studies show that LCFAOD still represents an important cause of morbidity and mortality, especially in China, Australia, Germany, and the United States. An accurate diagnosis remains challenging, and thus the timely and potentially life-saving initiation of treatment; hence a simple, minimally invasive newborn screen may constitute an important medical advance.
“This study may help in enhancing overall awareness of disorders of mitochondrial carnitine–acylcarnitine cycle through clarifying the signification of early diagnosis and proper treatment on the prevention and recovery of patients,” the authors concluded.
Zhou D, Cheng Y, Yin X, et al. Newborn screening for mitochondrial carnitine-acylcarnitine cycle disorders in Zhejiang province, China. Front Genet. Published online March 14, 2022. doi:10.3389/fgene.2022.823687