Prevalence of propionic acidemia in China

Abstract

Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid (2MCA), propionylglycine, glycine and 3-hydroxypropionate can be used to diagnose PA. Early-onset PA can lead to acute deterioration, metabolic acidosis, and hyperammonemia shortly after birth, which can result in high mortality and disability. Late-onset cases of PA have a more heterogeneous clinical spectra, including growth retardation, intellectual disability, seizures, basal ganglia lesions, pancreatitis, cardiomyopathy, arrhythmias, adaptive immune defects, rhabdomyolysis, optic atrophy, hearing loss, premature ovarian failure, and chronic kidney disease. Timely and accurate diagnosis and appropriate treatment are crucial to saving patients’ lives and improving their prognosis. Recently, the number of reported PA cases in China has increased due to advanced diagnostic techniques and increased research attention. However, an overview of PA prevalence in China is lacking. Therefore, this review provides an overview of recent advances in the pathogenesis, diagnostic strategies, and treatment of PA, including epidemiological data on PA in China. The most frequent variants among Chinese PA patients are c.2002G > A in PCCA and c.1301C > T in PCCB, which are often associated with severe clinical symptoms. At present, liver transplantation from a living (heterozygous parental) donor is a better option for treating PA in China, especially for those exhibiting a severe metabolic phenotype and/or end-organ dysfunction. However, a comprehensive risk–benefit analysis should be conducted as an integral part of the decision-making process. This review will provide valuable information for the medical care of Chinese patients with PA.

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“…Consequently, the utilization of DBS methylmalonic acid and homocysteine may be extended to encompass follow-up monitoring of MMA patients. Furthermore, methylcitrate and 3-hydroxypropionic acid are recognized for their heightened specificity in PA diagnosis relative to propionylcarnitine (41). In our current investigation, significant associations were observed among DBS methylcitrate, propionylcarnitine, and 3-hydroxypropionic acid in follow-up PA patients, with a notable linear correlation between DBS and urine methylcitrate.…”

The utility of methylmalonic acid, methylcitrate acid, and homocysteine in dried blood spots for therapeutic monitoring of three inherited metabolic diseases

“…Consequently, the utilization of DBS methylmalonic acid and homocysteine may be extended to encompass follow-up monitoring of MMA patients. Furthermore, methylcitrate and 3-hydroxypropionic acid are recognized for their heightened specificity in PA diagnosis relative to propionylcarnitine ( 41 ). In our current investigation, significant associations were observed among DBS methylcitrate, propionylcarnitine, and 3-hydroxypropionic acid in follow-up PA patients, with a notable linear correlation between DBS and urine methylcitrate.…”

Fasting alleviates metabolic alterations in mice with propionyl-CoA carboxylase deficiency due to Pcca mutation

“…Decreased PCC activity disrupts the conversion of propionyl-CoA into methylmalonyl-CoA and its subsequent entry into the tricarboxylic acid (TCA) cycle, an anaplerotic process within mitochondria. The advancement of PA can give rise to a range of complications, and inadequate management of this condition poses life-threatening risks 1 – 11 .…”

“…Propionate, odd-chain fatty acids, side-chain of cholesterol, and propiogenic amino acids such as valine, isoleucine, methionine, and threonine are all metabolic precursors of propionyl-CoA 5 , 11 . Any modulation of the metabolism of these compounds linked to propionyl-CoA will impact PA.…”