Propionic and Methylmalonic Acidemias: Initial Clinical and Biochemical Presentation

Abstract

PA and MAA have numerous nonspecific presentations, potentially leading to delayed diagnosis or misdiagnosis. In this paper, we present the clinical and biochemical characteristics of MMA and PA patients at initial presentation. Results. This is a retrospective review of 20 patients with PA ( n = 10 ) and MMA ( n = 10 ). The most observed symptoms were vomiting (85%) and refusing feeding (70%). Ammonia was 108.75 ± 9.3 μmol/l, showing a negative correlation with pH and bicarbonate and positive correlation with lactate and anion gap. Peak ammonia did not correlate with age of onset ( r = 0.11 and p = 0.64 ) or age at diagnosis ( r = 0.39 and p = 0.089 ), nor did pH ( r = 0.01 , p = 0.96 ; r = − 0.25 , p = 0.28 ) or bicarbonate ( r = 0.07 , p = 0.76 ; r = − 0.22 , p = 0.34 ). There was no correlation between ammonia and C3 : C2 ( r = 0.1 and p = 0.96 ) or C3 ( r = 0.23 and p = 0.32 ). The glycine was 386 ± 167.1 μmol/l, and it was higher in PA ( p = 0.003 ). There was a positive correlation between glycine and both pH ( r = 0.56 and p = 0.01 ) and HCO3 ( r = 0.49 and p = 0.026 ). There was no correlation between glycine and ammonia ( r = − 0.435 and p = 0.055 ) or lactate ( r = 0.32 and p = 0.160 ). Conclusion. Clinical presentation of PA and MMA is nonspecific, though vomiting and refusing feeding are potential markers of decompensation. Blood gas, lactate, and ammonia levels are also good predictors of decompensation, though increasing levels of glycine may not indicate metabolic instability.

Case report: A unusual case of delayed propionic acidemia complicated with subdural hematoma

“…an accessory pathway. This causes circulatory, neurological, endocrine, and other systems to also be impaired (3,5).…”

“…Therefore, the pathological characteristics of myopathy caused by PA are similar to those of metabolic myopathy, which are characterized mainly by different sizes of muscle fibers, scattered distributions of vacuoles and cracks, and uneven enzyme activity in the cytoplasm. The ragged red fiber (RRF) and strong subdural hematoma (SDH)reactive blood vessels (SSV) phenomena are evident in some patients (5).…”

Fasting alleviates metabolic alterations in mice with propionyl-CoA carboxylase deficiency due to Pcca mutation

“…Decreased PCC activity disrupts the conversion of propionyl-CoA into methylmalonyl-CoA and its subsequent entry into the tricarboxylic acid (TCA) cycle, an anaplerotic process within mitochondria. The advancement of PA can give rise to a range of complications, and inadequate management of this condition poses life-threatening risks [1][2][3][4][5][6][7][8][9][10][11] .While the precise pathological mechanisms underlying various complications associated with PA remain incompletely understood, it is clear that the accumulation of propionyl-CoA and its toxic metabolites plays a significant role as pathogenic factors. This is primarily due to the structural similarity between acetyl-CoA (C2 CoA) and propionyl-CoA (C3 CoA), where the increased levels of C3 CoA can result in metabolic crises through competition with C2 CoA.…”

“…Decreased PCC activity disrupts the conversion of propionyl-CoA into methylmalonyl-CoA and its subsequent entry into the tricarboxylic acid (TCA) cycle, an anaplerotic process within mitochondria. The advancement of PA can give rise to a range of complications, and inadequate management of this condition poses life-threatening risks [1][2][3][4][5][6][7][8][9][10][11] .…”