Central Precocious Puberty in a Chinese Girl with cblC-Type Methylmalonic Acidemia: a case report

Abstract

Background Cobalamin C-type methylmalonic acidemia (cblC-type MMA) is an autosomal-recessive genetic disease characterized by intracellular cobalamin (vitamin B12) metabolic disorder caused by MMACHC mutations. cblC-type MMA has diverse clinical manifestations due to the dysfunction of multiple organs. Central precocious puberty (CPP) is caused by early activation of the hypothalamus-pituitary-gonad axis before 8 years of age for girls and 9 years of age for boys. Case presentation: A Chinese girl was diagnosed with cblC-type MMA at 33 days old with elevated serum levels of methylmalonic acid and homocysteine. Genetic screening revealed compound heterozygous mutations in exon 4 of the MMACHC gene, the variants were c.445_446insA (p.C149XfsX1) inherited from father and c.609G > A (p.W203X) inherited from the mother. She was treated with special formula powder (isoleucine, methionine, threonine and proline removed) and an intramuscular injection of hydroxycobalt ammonium, oral L-carnitine and betaine after diagnosis. She showed breast development, elevated baseline levels of sex hormones and increased uterine volume at 7 years and 9 months of age, and CPP was definitively diagnosed. Gonadotrophin releasing hormone analogue (GnRHa) and rhGH were used to protect growth for the patient without obvious side effects up to date. Conclusions Abnormal metabolites of methionine due to MMACHC gene mutations, may lead to CPP in children with MMA. For patients diagnosed with both MMA and CPP, combined treatment with GnRHa and rhGH may be safe and sufficient to improve adult height.