Methylmalonic acidemia/propionic acidemia – the biochemical presentation and comparing the outcome between liver transplantation versus non-liver transplantation groups

Abstract

Background Most patients with isolated methylmalonic acidemia (MMA) /propionic acidemia (PA) presenting during the neonatal period with acute metabolic distress are at risk for death and significant neurodevelopmental disability. The nationwide newborn screening for MMA/PA has been in place in Taiwan from January, 2000 and data was collected until December, 2016. Results During the study period, 3,155,263 newborns were screened. The overall incidence of MMA mutase type cases was 1/121,356 ( n = 26), 1 cobalamin B was detected and that for PA cases ( n = 4) was 1/788,816. The time of referral is 8.8 days for MMA patients, and 7.5 days for PA patients. The MMA mutase type patients have higher AST, ALT, and NH 3 values as well as a lower pH value ( p < 0.05). The mean age for liver transplantation (LT) is 402 days (range from 0.6–6.7 yr) with 16 out of 20 cases (80.0%) using living donors. The mean admission length shortened from 90.6 days/year (pre-LT) to 5.3 days/year (at 3rd year post-LT) ( p < 0.0005). Similarly, the tube feeding ratio decreased from 67.8 to 0.50% ( p < 0.00005). The anxiety level of the caregiver was reduced from 33.4 to 27.2 after LT ( p = 0.001) and the DQ/IQ performance of the patients was improved after LT from 50 to 60.1 ( p = 0.07). Conclusion MMA/PA patients with LT do survive and have reduced admission time, reduced tube feeding and the caregiver is less anxious.

Dual mRNA therapy restores metabolic function in long-term studies in mice with propionic acidemia

“…However, these primary disease biomarkers were not normalized to levels observed in unaffected mice. This is consistent with the liver transplantation experience in patients with PA, which show a reduction, but not full normalization, of metabolite profiles post transplant 27 , 28 , 33 due to the accumulation of disease-associated metabolites in extrahepatic tissues, such as skeletal muscle. Although liver transplantation does not completely normalize disease-associated metabolites, it has been shown to improve clinical outcomes, specifically significantly reducing the occurrence of life-threatening metabolic decompensations, improving the overall quality of life, and improving cardiac function in patients with PA 27 , 28 , 33 .…”

Promoterless, Nuclease‐Free Genome Editing Confers a Growth Advantage for Corrected Hepatocytes in Mice With Methylmalonic Acidemia

“…The high mortality and morbidity of classical MMA has led to the use of liver transplantation as an elective surgical intervention, even in young children [20][21][22]. Liver transplantation can stabilize MMA patients, greatly reduces metabolite burden, and eliminates metabolic crises [22][23][24][25][26]. However, as transplantation procedures bear grave risks and complications [27], an alternative to early liver transplantation that is less invasive, durable, and therapeutic would represent an important new treatment for classical MMA.…”

Liver transplantation in children with inborn errors of metabolism: 30 years experience in NSW, Australia

“…In our cohort diets were liberalized cautiously and were individualized for each patient. A similar approach was noted in two studies conducted analyzing the data of patients with OA who underwent LT 20,21 …”