A Rare Case of Malonic Aciduria Diagnosed by Newborn Screening in Qatar

Mamatha Ramaswamy,Victor Skrinska,Rola Mitri,Ravi Joshi,Laila Mahmoud Ahmed,Ghassan Abdoh

doi:10.3390/ijns3010005

Mamatha Ramaswamy, Victor Skrinska + Show 4 more

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https://doi.org/10.3390/ijns3010005

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Abstract

Malonic aciduria is a rare autosomal recessive organic acid disorder. With the widespread use of tandem mass spectrometry for analysis of the amino acid/acylcarnitine profile on dried blood spots for newborn screening (NBS), this condition can be readily diagnosed and can be included in the organic acid screen in NBS programs. In Qatar, we report the first case of an asymptomatic baby screened and diagnosed with malonic aciduria through NBS. This patient has a genetic variant of malonyl-CoA decarboxylase that has not been previously reported in the literature. This condition should be differentiated from a similar disorder, combined malonic and methylmalonic aciduria. The clinical phenotype of malonic aciduria is variable and the pathophysiology is not fully understood. There is no established guidance or recommendations regarding the appropriate treatment regimen, dietary therapy or regular follow-up of these patients. Most available evidence for treatment is based on a single study or case report.

Highlights

Malonic aciduria is caused by malonyl-CoA decarboxylase (MCD) deficiency
With the widespread use of tandem mass spectrometry methods for amino acid/acylcarnitine (AA/AC) screening on dried blood spots (DBS) by many newborn screening laboratories around the world, we are likely to be faced with the challenges of diagnosing such rare inborn errors of metabolism in our NBS programs
For the NBS laboratories participating in the Region 4 Genetics Collaborative (R4GC) or the Mayo Clinic Collaborative Laboratory Integrated Reports (CLIR), the AA/AC profile results can be uploaded and compared to normal populations and previously reported abnormal results for specific metabolic disorders to further support the suspicion of a specific metabolic disorder

Summary

Introduction

Malonic aciduria is caused by malonyl-CoA decarboxylase (MCD) deficiency. It is a rare autosomal recessive disorder and until now fewer than 30 cases have been reported in the literature [1]. Cytoplasmic malonyl-CoA is a potent inhibitor of carnitine palmitoyltransferase (CPT1) and, of mitochondrial fatty acid oxidation [5]. The balance of malonyl-CoA synthesis by acetyl-CoA carboxylase and degradation by MCD is likely to have an important regulatory role in fatty acid metabolism. Increased malonyl-CoA levels potently inhibit long-chain acylcarnitine acyltransferases [5] and decrease the β-oxidation of fatty acids in both mitochondria and peroxisomes. The MLYCD gene has a tissue-specific expression [5] and decrease the β-oxidation of fatty acids in both mitochondria and peroxisomes.

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