Background <p><i>CARS1</i> loss of function compound heterozygous or homozygous variants have been reported in five individuals to cause a neurodevelopmental phenotype that includes microcephaly and brittle hair and nails. Additional multisystem involvement in these five people have included neurologic, cardiac, ophthalmologic and endocrine problems.</p> Case presentation <p>We report a sixth person with novel compound heterozygous variants in <i>CARS1</i>. In addition to the previously reported features such as intellectual disability, neurologic features, microcephaly and hair abnormalities, this patient had persistent hypoglycemia due to congenital hyperinsulinism.</p> Conclusions <p>This report identifies two novel variants in <i>CARS1</i> and expands the phenotype of this multisystem disorder to include congenital hyperinsulinism.</p>