[Mutation analysis for a family affected with riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency].

Abstract

OBJECTIVE:

To identify pathogenic mutation in a boy affected with riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency (RR-MADD).

METHODS:

The patient was initially diagnosed as primary carnitine deficiency (PCD) and has been treated with carnitine supplementation for 7 years. Clinical manifestations and characteristics of fibula muscle specimen were analyzed. Potential mutation in electron transfer flavoprotein dehydrogenase (ETFDH) gene (for the patient and his parents) and carnitine transfer protein gene (SLC22A5) (for the patient) was screened.

RESULTS:

Electronic microscopy of the muscle specimen has suggested lipid storage myopathy. Mutation analysis has found that the patient carried compound heterozygous mutations, c.250G>A and c.380T>C, in exon 3 of the ETFDH gene, whilst his father and mother were heterozygous for the c.380T>C and c.250G>A mutations, respectively. Screening of the SLC22A5 gene has yielded no clinically meaningful result. After the establishment of diagnosis of RR-MADD, the condition of the patient has improved greatly with supplementation of high doses of riboflavin along with continuous carnitine supplement.

CONCLUSION:

The c.250G>A (p.Ala84Thr) mutation of exon 3 of the ETFDH gene has been a hot spot in Southern Chinese population, whilst the c.380T>C (p.Leu127Pro) is rarely reported. Our case has suggested that therapeutic diagnosis cannot substitute genetic testing. The mechanism for having stabilized the patient with only carnitine supplementation for 7 years needs further investigation.

• Authors: Jun Lu, Lijuan Ji
• Journal: Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics (Zhonghua Yi Xue Yi Chuan Xue Za Zhi) Vol. 31 Issue 4 Pg. 428-32 (Aug 2014) ISSN: 1003-9406 [Print] China
• PMID: 25119904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Electron-Transferring Flavoproteins
• Iron-Sulfur Proteins
• Organic Cation Transport Proteins
• SLC22A5 protein, human
• Solute Carrier Family 22 Member 5
• Oxidoreductases Acting on CH-NH Group Donors
• electron-transferring-flavoprotein dehydrogenase
• Riboflavin

Topics

• Adolescent
• Adult
• Base Sequence
• Child
• DNA Mutational Analysis
• Electron-Transferring Flavoproteins (genetics, metabolism)
• Female
• Humans
• Iron-Sulfur Proteins (genetics, metabolism)
• Male
• Molecular Sequence Data
• Multiple Acyl Coenzyme A Dehydrogenase Deficiency (enzymology, genetics, metabolism)
• Muscle, Skeletal (metabolism)
• Organic Cation Transport Proteins (genetics, metabolism)
• Oxidoreductases Acting on CH-NH Group Donors (genetics, metabolism)
• Riboflavin (metabolism)
• Solute Carrier Family 22 Member 5