Supplementary Material for: Two Siblings With LRPPRC Mutation: Mitochondrial Complex IV Deficiency: Case Report

Objectives: Mitochondrial diseases caused by mutations in the LRPPRC gene are rare and leading to multisystemic dysfunction. We report two siblings from consanguineous Iraqi parents, both harboring a rare homozygous deletion in LRPPRC (c.2726_2728del; p.Lys909del), previously reported in one other patient. These cases contribute to the expanding phenotypic and geographic spectrum of LRPPRC-related mitochondrial disease.
Case presentation: The younger sibling, a 9-year-old girl, presented with severe growth retardation, global developmental delay, hypotonia, spastic ataxic gait and lactic acidosis. MRI showed symmetrical hyperintensities in the mesencephalon and thalami, cerebellar atrophy and an inverted lactate peak on MR spectroscopy. Hypertrophic cardiomyopathy was also detected. The older sibling, aged 13, exhibited milder manifestations including axial hypotonia, tremor, ataxia and persistent hyperlactatemia. Both siblings had elevated lactate levels, but otherwise normal metabolic panels.
Conclusions: These cases highlight the clinical variability of LRPPRC-related disorders. Our report underscores the importance of considering LRPPRC mutations in the differential diagnosis of early-onset neurodevelopmental delay, multisystemic dysfunction with lactic acidosis, especially in populations with high rates of consanguinity. Early genetic diagnosis via whole exome sequencing is essential for accurate diagnosis, genetic counseling and family planning.