Clinical, Genetic and Magnetic Resonance Findings in an Infant Affected by Propionic Acidemia

Purpose: Report an infant patient of propionic acidemia with two mutations in the PCCB gene identified by genetic diagnosis. Method: The patient received gas chromatograph-mass spectrometry and liquid chromatography-tandem mass spectrometry examination, electroencephalogram (EEG), MRI and genetic tests. He was diagnosed as propionic academia. Results: The boy was admitted in hospital at 8 months of age because of dyspnea, depression, seizures. The EEG was abnormal. MRI showed abnormal signal in bilateral basal ganglia. The gas chromatograph-mass spectrometry and liquid chromatography-tandem mass spectrometry showed glycine, 3-hydroxypropionate, tiglyglycine, methylcitric acid, propionyl carnitine increased. The genetic tests demonstrated that the patient carried the mutations c.337C>T and c.1127 G>T in the PCCB gene. The mutations were inherited from his parents individually. Conclusion: The patient carried two compound heterozygous mutations in PCCB gene which resulted in propionic academia. The metabolomics screen and brain MRI also played significant roles in the diagnosis of propionic acidemia. Figure 1: Brain MR images of the baby boy at the age of 8 months with propionic acidemia. T2-weighted cranial magnetic resonance image showed bilateral symmetrical increased signal in the basal ganglia, including lentiform nucleus (black arrows), the head of caudate nucleus (white arrows). Citation: Cheng Y, Yu D, Ning G, Qu H, Zhao F, et al. (2017) Clinical, Genetic and Magnetic Resonance Findings in an Infant Affected by Propionic Acidemia. J Mol Genet Med 11: 273 doi:10.4172/1747-0862.1000273 Volume 11 • Issue 2 • 1000273 J Mol Genet Med, an open access journal ISSN: 1747-0862 Page 2 of 3 weighted images (Figure 1) and decreased signal in T1-weighted images (Figure 2). The diffuse cortical atrophy and enlarged subarachnoid space were demonstrated. The diffusional weighted images (DWI) showed abnormal signal in the basal ganglia and the genu of the corpus callosum (Figure 3). The urine metabolic test showed glycine, 3-hydroxypropionate, tiglyglycine, methylcitric acid increased. The blood metabolic screen showed phenylalanine (Phe) (was 99.509), glycine (Gly)/alanine (Ala) (was 3.234), Phe/tyrosine (Tyr) (was 2.106), C3 (was 46.997), C5DC (was 0.096), C0/C16 (was 91.477), C3/C0 (was 2.764), C3/C2 (was 5.357), C3/C16 (was 252.865), C5DC/C16 (was 0.371), C8/C16 (was 0.932) increased; leucine (Leu)/Phe (was 0.671), valine (Val)/Phe (was 1.231), C4/C3 (was 0.006) decreased. Combined with the results of blood and urine metabolic screening, the patient was suspected to have PPA. The patient’s disease was resulted from the compound heterozygous Figure 2: T1-weighted cranial magnetic resonance image showed bilateral symmetrical decreased signal in the basal ganglia, including lentiform nucleus (black arrows) and the head of caudate nucleus (white arrows). The enlarged subarachnoid space and lateral fissures suggested the cerebral atrophy. Figure 3: Diffusion-weighted image showed abnormal signal and in the lentiform nucleus (black arrows) and the genu of the corpus callosum (empty arrow). Gene location Chromosomal location Nucleotide changes Amino acid changes rs code Heterozygosis/homozygosis PCCB chr3:135975430 c.337C>T(E3) p.113R>X rs186031457 Heterozygosis chr3:136045681 c.1127G>T(E11) p.376R>L rs142982097 Heterozygosis Table 1: Information of the proband’s mutations identified in the PCCB gene. No. Gene location Nucleotide changes Amino acid changes rs code Heterozygosis/homozygosis 1* PCCB c.337C>T p.113X rs186031457 Heterozygosis 2* PCCB c.1127G>T p.376L rs142982097 Heterozygosis Note: 1*: The proband’s father; 2*: The proband’s mother Table 2: Information of the parents’ mutations identified in the PCCB gene. mutations c.337C>T and c.1127G>T in the PCCB gene (Table 1). The parents carried the mutations identified in the PCCB gene (Table 2). The mutation named c.337C>T inherited from her father was a nonsense mutation. The mutation named c.1127G>T was inherited from her mother. The compound mutations can cause the amino acid change. Early effective fluid infusion, protecting of important organs, proper use of arginine to reduce the blood ammonia correction of electrolyte imbalance and acidosis effective antiepileptic drugs were helpful for saving life. Also, the patient received low protein and high calorie diet. After the prompt treatment, the epileptic seizures were controlled, and the serum biochemical parameters returned to normal. Blood ammonia level was decreased to 41.6 umol/L.