Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China

Abstract

BackgroundTandem mass spectrometry (MS/MS) has been available in China for 8 years. This technique makes it possible to screen for a wide range of previously unscreened inborn errors of metabolism (IEM) using a single test. This 3-year pilot study investigated the screening, diagnosis, treatment and outcomes of IEM in symptomatic infants and children.MethodsAll children encountered in the Newborn Screening Center of Zhejiang Province during a 3-year period with symptoms suspicious for IEM were screened for metabolic diseases. Dried blood spots were collected and analyzed by tandem mass spectrometry. The diagnoses were further confirmed by clinical symptoms and biochemical analysis. Neonatal intrahepatic cholestasis caused by citrin deficiency, ornithine transcarbamylase deficiency and primary carnitine deficiency were confirmed by DNA analysis.ResultsA total of 11,060 symptomatic patients (6,720 boys, 4,340 girls) with a median age of 28.8 months (range: 0.04-168.2 months) were screened. Among these, 62 were diagnosed with IEM, with a detection rate of 0.56%. Thirty-five were males and 27 females and the median age was 3.55 months (range 0.07-143.9 months). Of the 62 patients, 27 (43.5%) had aminoacidemias, 26 (41.9%) had organic acidemias and nine (14.5%) had fatty acid oxidation disorders.ConclusionsBecause most symptomatic patients are diagnosed at an older age, mental retardation and motor delay are difficult to reverse. Additionally, poor medication compliance reduces the efficacy of treatment. More extensive newborn screening is thus imperative for ensuring early diagnosis and enhancing the treatment efficacy of IEM.

Applying targeted next generation sequencing to dried blood spot specimens from suspicious cases identified by tandem mass spectrometry-based newborn screening

“…For instance, the highest published prevalence of CUD in the Southern China was 1:32,354, whereas four cases have already been identified merely from the CDI cases out of a population of 81,664 in the Northern China [18]. Several other identified diseases follow similar prevalence pattern [18,21,22].…”

“…Compared to the sophisticated TMS applications in expanded NBS in developed countries [1,3,4], China has been making great efforts to explore, evaluate, and implement TMS screening since 2003 [18,21,22]. At present, China has an estimated national coverage of 20%, concentrated in well-developed provinces and cities [21,22].…”

“…At present, China has an estimated national coverage of 20%, concentrated in well-developed provinces and cities [21,22].…”

“…On the other hand, many IEMs are clinically heterogeneous that the molecular diagnosis is not always practically helpful [34] because of the imperfect penetrance of each individual genotype. It has been reported that the implementation of TMS screening program has led to more identified cases bearing certain disorders of which most subjects are asymptomatic throughout their life [9,[20][21][22]. The environmental/maternal/ethnic effect as well as miscellaneous manifestation also complicated the genotype/phenotype correlation [35][36][37][38].…”

Inborn Errors of Metabolism-Clinical Findings and Laboratory Tests at the Children’s Medical Center, Tehran, Iran

“…In many cases, prevention of mortality and neurologic sequelae depends on early diagnosis and proper treatment at an early age (8). Recent advances in laboratory methods, pre-birth screening, and early diagnosis and treatment have significantly reduced the morbidity and mortality rates (9)(10)(11). The most common disorders are Wilson's disease, glycogen storage disease, mucopolysaccharidosis, and galactosemia (12).…”