Neonatal-onset cblC-type methylmalonic acidemia combined with homocysteinemia: case report

To investigate the clinical diagnostic features, screening and definitive diagnostic methods of neonatal-onset cblC type methylmalonic acidemia (MMA) combined with homocysteinemia, so as to provide a reference for early clinical identification and diagnosis of this disease.

The clinical data of 1 neonate with neonatal-onset cblC type MMA combined with homocysteinemia admitted to our hospital were retrospectively analyzed. Routine laboratory tests, blood tandem mass spectrometry, serum homocysteine test, urinary organic acid analysis, cranial MRI and genetic testing were performed on the neonate. Combined with relevant literature, the clinical features, diagnostic strategies, treatment and prognosis of the disease were reviewed and summarized.

The patient was a 20-day-old male neonate, presenting with persistent feeding difficulty and weak response after birth as the main manifestations, accompanied by hypotonia and diminished primitive reflexes, without typical critical signs. Laboratory examinations showed significantly elevated serum homocysteine; blood tandem mass spectrometry revealed increased propionylcarnitine, elevated C3/C2 ratio and decreased methionine; urinary organic acids showed increased methylmalonic acid and methylcitric acid. Cranial MRI showed hyperintensity in the bilateral globus pallidus on T1WI. Genetic testing identified two heterozygous pathogenic variants, c.567dupT and c.609G>A, in the MMACHC gene of the neonate, inherited from the mother and father respectively, conforming to the autosomal recessive inheritance pattern. The patient was finally diagnosed with cblC type MMA combined with homocysteinemia.

Neonatal-onset cblC type MMA combined with homocysteinemia has insidious and non-specific clinical manifestations, which are easily confused with other neonatal diseases, leading to missed diagnosis and misdiagnosis. For neonates with unexplained feeding difficulty, poor mental response and abnormal muscle tone, timely metabolic screening including blood tandem mass spectrometry, urinary organic acid analysis and serum homocysteine test should be conducted. Genetic testing is the gold standard for the definitive diagnosis and classification of this disease, and can also provide a basis for genetic counseling and prenatal diagnosis. The implementation of neonatal screening for inherited metabolic diseases and the establishment of a multidisciplinary collaborative diagnosis and treatment model are the keys to achieving early diagnosis and treatment of this disease and improving the prognosis of patients.