Identification of MMACHC and PROKR2 mutations causing coexistent cobalamin C disease and Kallmann syndrome in a young woman

Cobalamin C (cblC) disease and Kallmann syndrome (KS) are rare hereditary diseases. To date, no report has described the coexistence of those two genetic disorders in the same patient, or an association between them. We report the case of a 23-year-old woman with cblC defect and KS. She first presented mild memory problems in puberty, which worsened in adulthood to progressive memory loss accompanied by slow and unsteady walking, slow response, inattention, cognitive impairment, insomnia, no sense of smell, and the lack of spontaneous puberty. Laboratory tests revealed gonadotropin deficiency, a low estrogen level, and remarkably elevated serum homocysteine and serum and urine organic acid levels. Whole-exome sequencing detected compound heterozygous variants in MMACHC [c.398_399del (p.Gln133Argfs*4) and c.482G > A (p.Arg161Gln)] and heterozygous variants in PROKR2 [c.337T > C (p.Tyr113His)]. Thus, clinical and genetic examinations confirmed the cblC disease and KS diagnoses. This report on coexisting cblC disease and KS caused by different pathogenic genes in a single patient enriches the clinical research on these two rare genetic diseases.