Case Report: A Case of β-Ureidopropionase Deficiency Complicated With MELAS Syndrome Caused by UPB1 Variant and Mitochondrial Gene Variant

Abstract

Backgroundβ-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder caused by genetic defects in mitochondrial DNA.Case PresentationOne 8-year-old boy presented with dizziness, vomiting, and convulsions. The gas chromatography–mass spectrometry results suggested β-ureidopropionase deficiency. The whole-exome sequencing results revealed homozygous missense variant c.977G>A (p.R326Q) in UPB1. However, the patient presented with persistent hyperlactacidemia and metabolic acidosis, which did not correspond to the classic features of β-ureidopropionase deficiency. Combined with the manifestations of developmental delay, poor academic performance, and poor sports stamina, whole-mitochondrial-genome sequencing was performed. The results exhibited the variant m.3243A>G of MT-TL1 gene. The level of heterogeneity was 65% in the patient and 17.8% in his mother. Eventually, the final diagnosis of β-ureidopropionase deficiency combined with MELAS syndrome was made.ConclusionThe report about β-ureidopropionase deficiency caused by a nuclear gene variant and MELAS syndrome caused by a mitochondrial gene variant coexisting in the same patient enriches the clinical study of these two rare diseases.

Commentary: Point Prevalence and Associated Factors of Hip Displacement in Pediatric Patients With Mitochondrial Disease

“…We do not agree that the family history for genetic or metabolic disorders was negative (1). The mother of the index patient was of short stature (146 cm) and was carrying the mtDNA variant m.3243A>G with a heteroplasmy rate of 17% (1). According to this constellation, the mother also had a mild MELAS syndrome.…”

“…We read with interest the article by Shu et al about an 8-year-old boy with double trouble mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome due to the mtDNA variant m.3243A>G in MT-TL1 with a heteroplasmy rate of 65% and β-ureidopropionase deficiency due to the homozygous variant c.977G>A in UPB1 ( 1 ). MELAS phenotypically manifested with developmental delay, epilepsy, a stroke-like lesion (SLL), lactic acidosis, exercise intolerance, myopathy, basal ganglia calcification, hearing loss, and cognitive decline ( 1 ). β-ureidopropionase deficiency only manifested with increased amino acids in urine ( 1 ).…”

“…MELAS phenotypically manifested with developmental delay, epilepsy, a stroke-like lesion (SLL), lactic acidosis, exercise intolerance, myopathy, basal ganglia calcification, hearing loss, and cognitive decline ( 1 ). β-ureidopropionase deficiency only manifested with increased amino acids in urine ( 1 ). The study is appealing but raises concerns that need to be discussed.…”

“…There is a discrepancy between the description of the cerebral MRI in the text and the caption of Figure 2. In the main text, the MRI is described as “showing no specific findings” but Figure 2 shows an SLL in the right parieto-occipital distribution ( 1 ).…”

“…Ptosis as a manifestation of a seizure is quite uncommon ( 1 ). We should know if a video is available of those seizures manifesting with ptosis.…”