Clinical features and outcomes of patients with cblC type methylmalonic acidemia carrying <italic><bold>MMACHC</bold></italic> gene c.609G>A mutation

To explore the clinical features and long-term outcomes of patients with cblC type methylmalonic acidemia (MMA) carrying c.609G>A (p.W203X) mutation of gene. The clinical and laboratory findings of 720 patients with MMA carrying the c.609G>A mutation were retrospectively analyzed. There were 172 cases carrying homozygous mutations of c.609G>A (group A), 169 cases carrying compound heterozygous mutations of c.609G>A with c.482G>A (p.R161Q), c.80A>G or c.394C>T (p.R132X) (group B), and 379 cases carrying compound heterozygous mutations of c.609G>A with c.658_660delAAG(p.K220del), c.315A>Tor c.567dupT(p.I190fs13)(group C).The clinical manifestations, the level of blood acylcarnitine, homocysteine and urinary organic acid, and the therapeutic efficacy were compared among groups. Logistic regression was used to analyze the factors influencing the prognosis of patients. There were 306 patients (42.5%) detected from newborn screening, including 156 cases with disease onset; and 414 patients were not detected from the screening, among whom 10 cases were diagnosed by testing after the sibling confirmed, and the remaining 404 were clinical cases. In 560 patients with disease onset, the median onset age is (3 days to 20 years). The onset age of patients in group B was later than that in group A and group C (<0.01). Patients aged mostly manifested as vomiting, diarrhea, feeding difficulties and convulsions, while those year mostly manifested as movement disorders and mental retardation. Patients with renal disease all carried mutations of c.80A>G or c.482G>A, and patients with pulmonary hypertension all carried c.80A>G mutations. A total of 621 cases had long-term follow-up, 156 cases (25.1%) developed well, 433 cases (69.7%) had development delay and 32 cases (5.2%) died. The available data of 559 cases were analyzed by logistic regression, and the results showed that the neonatal screening, disease onset, age of onset and gene mutation site were significantly associated with the prognosis of patients (<0.05 or <0.01). The c.609G>A mutation in gene is associated with early-onset MMA, and most patients, clinical onset occurred within 1 month after birth. The neonatal screening and early treatment can improve the prognosis of patients,whereas clinical onset is unfavorable for prognosis. Patients with c.609G>A homozygous mutation have a worse prognosis than those with the compound heterozygous mutation of c.609G>A with other mutations.