Incidence of maple syrup urine disease, propionic acidemia, and methylmalonic aciduria from newborn screening data

Abstract

Incidence for the branched-chain intoxication-type disorders, maple syrup urine disease, propionic acidemia and methlymalonic aciduria is dependent on the population screened. Here newborn screening results from three world regions, state screening laboratories in the United States, a region in Germany and Kuwait provides new incidence numbers. Maple syrup urine disease incidence in the United States was calculated to be 1: 220219, in South-West Germany 1: 119573 (Germany nationwide 1:177978), and in Kuwait 1: 59426. Incidence of propionic acidemia alone is calculated to be 1: 242741 in the United States, 1: 284450 in South-West Germany (Germany nationwide 1:202617) and 1:59426 in Kuwait. Incidence of isolated methylmalonic aciduria alone is 1:69354 in the United States, 1:568901 in South-West Germany (Germany nationwide 1:159199) and 1: 19809 in Kuwait. In the United States several newborn screening laboratories combine their results for propionic acidemia and methylmalonic aciduria, and also include combined remethylation disorders in the respective category, resulting in an incidence of 1:50709. Combined evaluation of methylmalonic aciduria, propionic aciduria and combined remethylation disorders results in a similar incidence for Germany of 1:67539. This evaluation of newborn screening incidences reflects some population differences for three intoxication-type metabolic disorders. However, different sample sizes of the populations screened over different time periods, and differences in case definitions for methylmalonic acidurias have to be considered when interpreting these data.

Systematic literature review and meta-analysis on the epidemiology of methylmalonic acidemia (MMA) with a focus on MMA caused by methylmalonyl-CoA mutase (mut) deficiency

“…Our findings align well with epidemiological studies published by Peng et al [67] and Chapman et al [62] after our review was performed [62, 67] and the systematic literature review by the Spanish Health Technology Assessment Agency , which was conducted with the purpose of evaluating the effectiveness of newborn screening programs [68]. However, compared to this work, our review was not restricted to screening programs, therefore, it provides a more comprehensive overview on disease epidemiology.…”

“…In the region of MENA, the meta-analysis results indicated higher disease frequencies for MMA and its isolated form. These results are in line with the recent findings of Chapman et al (2018) who reported a detection rate of 5.05, 1.44 and 0.18 per 100,000 newborns of isolated MMA in Kuwait, United States and South-West Germany, respectively [62].…”

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

“…The prevalence of MSUD in the United States is estimated to be 1:200,000, though some populations have much higher incidence rates. Such populations include the Mennonite population, with a reported incidence as high as nearly 1:350; the Galician population in Spain, with an incidence of 1:52,500; and the Ashkenazi Jewish population [ 3 ].…”

Investigation of leucinuria as a marker of progression of type 2 diabetes mellitus

“…The reason could be similar to that of maple syrup disease where branched chain keto acid dehydrogenase dysfunction results in elevation of BCAA in serum and excretion of the same in urine. 21 The estimation of BCAA in serum requires a well equipped laboratory with much more expensive and advanced tests like HPLC, Nuclear magnetic resonance (NMR) spectroscopy 11 , Liquid chromatography-Mass spectrometry 12 . Qualitative estimation of leucine in urine by TLC is a simple and cheaper technique which could be an alternative for estimation of serum leucine.…”