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Glutaric aciduria type 1 in Korea: report of two novel mutations.

Park JD, Lim B, Kim KJ, Hwang YS, Kim SK, Kang SH, Cho SI, Park SS, Lee JS, Chae JH - J. Korean Med. Sci. (2010)

Bottom Line: Here, we present their rather atypical clinical presentations with genetic characteristics for the first time in Korea.One patient was a compound heterozygote for p.Ser139Leu and p.Asp220Tyr, and the other for p.Ser139Leu and Glu160X.The mutations of the two alleles (p.Asp220Tyr and p.Glu160X) were novel and reports of p.Ser139Leu were rare both in Western and other Asian populations.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Glutaric aciduria type I (GA I) is an autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase. Although over 400 patients confirmed as GA I have been reported, reports from the Asian population had contributed to the minor proportion. We recently diagnosed two cases of GA I confirmed with mutational analysis. Here, we present their rather atypical clinical presentations with genetic characteristics for the first time in Korea. Profound developmental delay from birth, association of hearing loss, and neurological improvement after surgical intervention, were considered to be different clinical features from most reported cases. One patient was a compound heterozygote for p.Ser139Leu and p.Asp220Tyr, and the other for p.Ser139Leu and Glu160X. The mutations of the two alleles (p.Asp220Tyr and p.Glu160X) were novel and reports of p.Ser139Leu were rare both in Western and other Asian populations. These might suggest different genetic spectrum of Korean GA I patients.

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Related in: MedlinePlus

Magnetic resonance imaging (MRI) findings and GCDH gene mutational analysis of two patients. (A) MRI of the patient 1. A T2-weighted axial image showing a large amount of subdural fluid collection with frontotemporal atrophy and high signal intensity in both basal ganglia. (B) A novel mutation from the patient 1. c.658G>T, heterozygote, p.Asp220Tyr. (C) MRI of the patient 2. Asymmetric subdural fluid collection suggesting hemorrhage with mild mass effect on a T2-weighted axial image. (D) A novel mutation from the patient 2. c.478C>T, heterozygote, p.Q160X.
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Figure 1: Magnetic resonance imaging (MRI) findings and GCDH gene mutational analysis of two patients. (A) MRI of the patient 1. A T2-weighted axial image showing a large amount of subdural fluid collection with frontotemporal atrophy and high signal intensity in both basal ganglia. (B) A novel mutation from the patient 1. c.658G>T, heterozygote, p.Asp220Tyr. (C) MRI of the patient 2. Asymmetric subdural fluid collection suggesting hemorrhage with mild mass effect on a T2-weighted axial image. (D) A novel mutation from the patient 2. c.478C>T, heterozygote, p.Q160X.

Mentions: A 10-month-old female infant was referred to our hospital for developmental delay and large head size. She was born to unrelated healthy parents after a 41-week pregnancy. Although she could smile responsively and feed well, complete head control had not been achieved. She had never suffered from metabolic decompensation episodes, such as mental deterioration or seizures associated with infection or fever. Brain magnetic resonance imaging (MRI) revealed large amounts of bilateral subdural fluid collection, cerebral atrophy, and high signal intensity in both basal ganglia (Fig. 1A). After surgical drainage of subdural fluids, recurrent subdural bleeding, systemic infection, decreased mentality, and seizures occurred. These symptoms were not easily controlled in the ensuing postoperative period. Under the suspicion of metabolic encephalopathies, urine organic acid analysis was conducted, which revealed high levels of GA (7,360.9 mM/M Cr, ref: <5.3) and 3-OH-GA (67.6 mM/M Cr ref: <4.2). We analyzed the GCDH gene and identified compound heterozygote mutations of p.Ser139Leu and p.Asp220Tyr (Fig. 1B). Her mother was a heterozygote carrier for p.Ser139Leu mutation and father was a heterozygote carrier for p.Asp220Tyr. Elder brother who was phenotypically normal did not harbor any of the two mutations.


Glutaric aciduria type 1 in Korea: report of two novel mutations.

Park JD, Lim B, Kim KJ, Hwang YS, Kim SK, Kang SH, Cho SI, Park SS, Lee JS, Chae JH - J. Korean Med. Sci. (2010)

Magnetic resonance imaging (MRI) findings and GCDH gene mutational analysis of two patients. (A) MRI of the patient 1. A T2-weighted axial image showing a large amount of subdural fluid collection with frontotemporal atrophy and high signal intensity in both basal ganglia. (B) A novel mutation from the patient 1. c.658G>T, heterozygote, p.Asp220Tyr. (C) MRI of the patient 2. Asymmetric subdural fluid collection suggesting hemorrhage with mild mass effect on a T2-weighted axial image. (D) A novel mutation from the patient 2. c.478C>T, heterozygote, p.Q160X.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2877240&req=5

Figure 1: Magnetic resonance imaging (MRI) findings and GCDH gene mutational analysis of two patients. (A) MRI of the patient 1. A T2-weighted axial image showing a large amount of subdural fluid collection with frontotemporal atrophy and high signal intensity in both basal ganglia. (B) A novel mutation from the patient 1. c.658G>T, heterozygote, p.Asp220Tyr. (C) MRI of the patient 2. Asymmetric subdural fluid collection suggesting hemorrhage with mild mass effect on a T2-weighted axial image. (D) A novel mutation from the patient 2. c.478C>T, heterozygote, p.Q160X.
Mentions: A 10-month-old female infant was referred to our hospital for developmental delay and large head size. She was born to unrelated healthy parents after a 41-week pregnancy. Although she could smile responsively and feed well, complete head control had not been achieved. She had never suffered from metabolic decompensation episodes, such as mental deterioration or seizures associated with infection or fever. Brain magnetic resonance imaging (MRI) revealed large amounts of bilateral subdural fluid collection, cerebral atrophy, and high signal intensity in both basal ganglia (Fig. 1A). After surgical drainage of subdural fluids, recurrent subdural bleeding, systemic infection, decreased mentality, and seizures occurred. These symptoms were not easily controlled in the ensuing postoperative period. Under the suspicion of metabolic encephalopathies, urine organic acid analysis was conducted, which revealed high levels of GA (7,360.9 mM/M Cr, ref: <5.3) and 3-OH-GA (67.6 mM/M Cr ref: <4.2). We analyzed the GCDH gene and identified compound heterozygote mutations of p.Ser139Leu and p.Asp220Tyr (Fig. 1B). Her mother was a heterozygote carrier for p.Ser139Leu mutation and father was a heterozygote carrier for p.Asp220Tyr. Elder brother who was phenotypically normal did not harbor any of the two mutations.

Bottom Line: Here, we present their rather atypical clinical presentations with genetic characteristics for the first time in Korea.One patient was a compound heterozygote for p.Ser139Leu and p.Asp220Tyr, and the other for p.Ser139Leu and Glu160X.The mutations of the two alleles (p.Asp220Tyr and p.Glu160X) were novel and reports of p.Ser139Leu were rare both in Western and other Asian populations.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Glutaric aciduria type I (GA I) is an autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase. Although over 400 patients confirmed as GA I have been reported, reports from the Asian population had contributed to the minor proportion. We recently diagnosed two cases of GA I confirmed with mutational analysis. Here, we present their rather atypical clinical presentations with genetic characteristics for the first time in Korea. Profound developmental delay from birth, association of hearing loss, and neurological improvement after surgical intervention, were considered to be different clinical features from most reported cases. One patient was a compound heterozygote for p.Ser139Leu and p.Asp220Tyr, and the other for p.Ser139Leu and Glu160X. The mutations of the two alleles (p.Asp220Tyr and p.Glu160X) were novel and reports of p.Ser139Leu were rare both in Western and other Asian populations. These might suggest different genetic spectrum of Korean GA I patients.

Show MeSH
Related in: MedlinePlus