Clinical finding of
cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different
inborn errors of metabolism (IEM). Metabolic
cutis laxa results from
Menkes syndrome, caused by a defect in the
ATPase copper transporting alpha (ATP7A) gene;
congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in
ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene;
pyrroline-5-carboxylate reductase 1 deficiency;
pyrroline-5-carboxylate synthase deficiency;
macrocephaly, alopecia, cutis laxa, and scoliosis (
MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations;
transaldolase deficiency caused by mutations in the
transaldolase 1 (TALDO1) gene;
Gerodermia osteodysplastica due to mutations in the
golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and
mitogen-activated pathway (MAP)
kinase defects, caused by mutations in several genes [
protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene,
GTPase (HRAS), B-Raf proto-oncogene,
serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene,
GTPase (KRAS), SOS Ras/Rho
guanine nucleotide exchange factor 2 (SOS2),
leucine rich repeat scaffold
protein (SHOC2), NRAS proto-oncogene,
GTPase (NRAS), and Raf-1 proto-oncogene,
serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of
inborn errors of metabolism associated with
cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl
coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix
enzyme that catalyzes the second step of the beta-oxidation spiral of
fatty acids and plays an important role in
amino acid catabolism, particularly
valine.