Mutations in the HADHB gene induce dysfunctions in the beta-oxidation of fatty acids and result in a MTP deficiency, which is characterized by clinical heterogeneity, such as cardiomyopathy and recurrent Leigh-like encephalopathy.
Pathogenic variants in the MTP genes (HADHA and HADHB) cause MTP deficiency, a rare autosomal recessive metabolic disorder characterized by phenotypic heterogeneity ranging from severe, early-onset, cardiac disease to milder, later-onset, myopathy and neuropathy.
Here, using whole exome sequencing (WES), we identified a compound heterozygote of c.407T>C (p.M136T) and c.421G>A (p.A141T) within HADHB in a Chinese MTP deficiency patient of neuromyopathic form.
Altogether, our results strongly suggest that, due to variable effects of HADHA and HADHB mutations on MTP abundance and residual activity, improvement of MTP deficiency in response to bezafibrate was achieved in a subset of responsive genotypes.
Thus, the present patients are the second and third cases of MTP deficiency associated with missense HADHB mutation and infantile onset hypoparathyroidism.
Although the number of patients is still limited, it is suggested that the phenotype is correlated with the genotype and a combination of two mutant alleles of the HADHB gene in MTP deficiency.