Prevalence of carriers of the most common medium-chain acyl-CoA dehydrogenase (MCAD) deficiency mutation (G985A) in The Netherlands

Vries, H. G. De; Niezen-Koning, Klary E.; Kliphuis, J. W.; Smit, G. P. A.; Scheffer, Hans; Kate, L. P. Ten

doi:10.1007/s004390050149

Cited by 22 publications

(21 citation statements)

References 5 publications

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“…Of 43 families identified by Roe and Coates,'6 one-third had one or more unexplained sibling death. 16 Iafolla and colleagues' 1994 study2' of 120 MCADD patients reported that 32% of patients had siblings who were either known to have MCADD or had died of SIDS. Of 57 cases collected prospectively by the British Pediatric Association Surveillance System between 1994 and 1996, five had siblings who died.…”

Section: Family Historymentioning

confidence: 99%

Medium chain acyl-CoA dehydrogenase deficiency: Human genome epidemiology review

Wang

Fernhoff

Harnnon

et al. 1999

Genetics in Medicine

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Medium chain acyl-CoA dehydrogenase (MCAD) is a tetrameric flavoprotein essential for the poxidation of medium chain fatty acids. MCAD deficiency (MCADD) is an inherited error of fatty acid metabolism. The gene for MCAD is located on chromosome one (lp31). One variant of the MCAD gene, G985A, a point mutation causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD protein, has been found in 90% of the alleles in MCADD patients identified retrospectively. There is a high frequency of MCADD among people of Northern European descent, which is believed to be due to a founder effect. MCADD is inherited in an autosomal recessive manner. Of patients clinically diagnosed with MCADD, 81% who have been identified retrospectively are homozygous for K304E, and 18% are compound heterozygotes for K304E. Clinical data on the probability of clinical disease indicates that MCADD patients are at risk for the following outcomes: hypoglycemia, vomiting, lethargy, encephalopathy, respiratory arrest, hepatomegaly, seizures, apnea, cardiac arrest, coma, and sudden and unexpected death. Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). Differences in clinical disease specific to allelic variants have not been documented. Factors that may increase risk for disease onset or modify disease severity are age when the first episode occurred, fasting, and presence of infection. Acute attacks must be treated immediately with appropriate intravenous doses of glucose. For those diagnosed, long-term management of the disease includes preventing stress caused by fasting and maintaining a highcarbohydrate, reduced-fat diet, and carnitine supplementation. Hospitalization costs attributable to morbidity and mortality from MCADD are unknown; MCADD is not a diagnosis in the International Classification of Disease, 10th Revision (ICD-10) codebook.Furthermore, the penetrance of the MCAD genotypes is unknown; there appears to be a substantial number of asymptomatic MCADD individuals and some uncertainty regarding which individuals will manifest symptoms and which individuals will remain asymptomatic. Several technologies are available to detect MCADD. Diagnostic technologies include DNA-based tests for K304E mutations using the polymerase chain reaction (PCR), and the detection of abnormal metabolites in urine. Screening technologies include tandem mass spectrometry (MS/MS), which detects abnormal metabolites mostly in blood. State programs are beginning to offer screening in newborns for MCADD using MS/MS. In addition, a private company currently offers voluntary supplemental newborn screening for MCADD to birthing centers. Genetics in Medicine, 1999:1(7):332-339.

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Section: Family Historymentioning

confidence: 99%

Medium chain acyl-CoA dehydrogenase deficiency: Human genome epidemiology review

Wang

Fernhoff

Harnnon

et al. 1999

Genetics in Medicine

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“…The frequencies of MCAD deficiency differ largely among different populations, being significantly high in some areas. In Great Britain the incidence has been estimated to be 1 in 6,400, in the Netherlands 1 in 14,000, Switzerland 1 in 10,000 (Matsubara et al, 1992;de Vries et al, 1996;Conne et al, 1995). Population screening among our closest ethnic neighbors the Finns shows a frequency 1 in 147,000 (Romppanen et al, 1998); in a geographically close region like St. Petersburg it is 1 in 27,000 (Levin et al, 1992).…”

Section: Introductionmentioning

confidence: 96%

Mutation 985A>G in the MCAD gene shows low incidence in Estonian population

et al. 2000

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“…In The Netherlands, the 985G4A carrier frequency was determined previously to be 1/59 (95% CI 1/50 -1/73). 9 Compared to neighbouring countries and areas (Belgium 1/77, Germany 1/116, Normandy 1/118, and the prevalence decreased in southern parts of Western Europe; 8 for an overview, see Wang et al 7 ), the frequency in our country was rather high. Unfortunately, the regional distribution of the 985G4A frequency in The Netherlands was not assessed in the previous study.…”

Section: Discussionmentioning

confidence: 99%

“…In the families from this cohort, the 985G4A allele frequency was 94%, which is in agreement with the estimate previously used in calculating the estimated prevalence. 9 Regional differences of MCAD deficiency prevalence in The Netherlands The regional prevalences of MCAD deficiency in The Netherlands are shown in Figure 2. Significant differences were found between the three geographic/historical regions (w 2 ¼ 14.4, P ¼ 0.001 at 2 df).…”

Section: Observed Prevalence Of Mcad Deficiency In the Netherlandsmentioning

confidence: 99%

“…Hence, the expected prevalence of MCAD deficiency among newborns in our country would be 1/12 100 (95% CI 1/8450 -1/18 500) under Hardy -Weinberg conditions. 9 The Netherlands has about 16 million inhabitants with more that 200 000 newborns each year, thus about 16 (10 -23) new cases are expected annually (CBS, Dutch Central Bureau for Statistics).…”

Section: Introductionmentioning

confidence: 99%

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The difference between observed and expected prevalence of MCAD deficiency in The Netherlands: a genetic epidemiological study

et al. 2005

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Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency is assumed to be the most common inherited disorder of mitochondrial fatty acid oxidation. Few reports mention the difference between the expected and observed prevalence of MCAD deficiency on the basis of the carrier frequency in the population. We performed a population-wide retrospective analysis of all known MCAD-deficient patients in The Netherlands. In this study, the observed prevalence of MCAD deficiency in The Netherlands was 1/27 400 (95% confidence interval (CI) 1/23 000 -1/33 900), significantly different from the expected prevalence of 1/12 100 (95% CI 1/8450-1/18 500). The observed prevalence of MCAD deficiency showed a remarkable north -south trend within the country. From the patients in this cohort, it can be observed that underdiagnosis contributes to a larger extent to the difference between the expected and observed prevalences of MCAD deficiency in our country, than reduced penetrance. We determined estimates of the segregation proportion in a cohort of 73 families under the assumption of complete ascertainment (p LM ¼ 0.41, 95% CI 0.31 -0.51) and single ascertainment (p D ¼ 0.28, 95% CI 0.19 -0.37). With the expectation -maximization algorithm, a third estimate was obtained (p EM ¼ 0.28, 95% CI 0.20 -0.37). The agreement between the latter two estimates supports incomplete selection and the segregation proportions were in agreement with normal mendelian autosomal recessive inheritance.

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Prevalence of carriers of the most common medium-chain acyl-CoA dehydrogenase (MCAD) deficiency mutation (G985A) in The Netherlands

Cited by 22 publications

References 5 publications

Medium chain acyl-CoA dehydrogenase deficiency: Human genome epidemiology review

Medium chain acyl-CoA dehydrogenase deficiency: Human genome epidemiology review

Mutation 985A>G in the MCAD gene shows low incidence in Estonian population

The difference between observed and expected prevalence of MCAD deficiency in The Netherlands: a genetic epidemiological study

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