Autosomal Recessive Mitochondrial Pyruvate Carrier Deficiency (MPYCD) via the MPC1 (BRP44L) Gene

Mitochondrial Pyruvate Carrier Deficiency (MPYCD) is a rare disorder of mitochondrial pyruvate oxidation (Bricker et al. 2012; Brivet et al. 2003). Biochemically, this disease is characterized by increases in serum pyruvate and lactate, a normal lactate/pyruvate ratio, and normal pyruvate dehydrogenase activity. Affected individuals may manifest symptoms such as severe neonatal encephalopathy, delayed psychomotor development without regression, epilepsy, and/or peripheral neuropathy. Although there are limited data regarding patients affected with MPYCD, the phenotypic spectrum of this disorder has been reported to range from a more moderate childhood disorder to a severe, fatal neonatal form.

As MPC1 (formerly BRP44L) gene defects have only recently been linked to MPYCD and few cases have been described to date, global incidence and long-term prognosis for this disease are currently unknown.

MPYCD is an autosomal recessive disorder caused by defects in the mitochondrial pyruvate carrier complex (Bricker et al. 2012; Herzig et al. 2012). The MPC1 gene encodes for an inner mitochondrial membrane protein that interacts with MPC2 (BRP44) to form the multimeric mitochondrial pyruvate carrier complex essential for transport of pyruvate into the mitochondria. Two pathogenic variants, both missense, have been documented for MPC1-associated MPYCD (Bricker et al. 2012).

At the present time, clinical sensitivity for MPC1-associated Mitochondrial Pyruvate Carrier Deficiency is difficult to estimate as fewer than ten cases have been described in the literature. Analytical sensitivity should be high as all of the few reported pathogenic variants are detectable by sequencing.

This test provides full coverage of all coding exons of the MPC1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).