Researchers demonstrated the effectiveness of triheptanoin in a neonate patient with a lethal form of long chain fatty acid oxidation disorder (LCFAOD) and published their results in Molecular Genetics and Metabolism.
The case report authored by Pomerantz and colleagues describes a female fetus that showed severe ventriculomegaly at the 20-week ultrasound. This finding led to genetic testing of the parents, which revealed a heterozygous genotype with pathogenic variants in both cases, consistent with a diagnosis of neonatal-onset carnitine palmitoyltransferase 2 (NO-CPT2) deficiency. The patient was delivered at 38 weeks of gestation.
Immediately after birth, the healthcare team initiated intravenous fluids rich in dextrose in the first hour, followed by the administration of triheptanoin boluses (4 g/kg) with polycal every 3 hours via an orogastric tube. After 24 hours, the dose increased to 7g/kg, and Vivonex®T.E.N. formula was added. During the first 3 weeks of life, feeding included progressive amounts of walnut oil to reintroduce long-chain fatty acids into the newborn’s diet.
“Here we report the first case of dual null variant [NO-CPT2] deficiency to survive the neonatal period and remain metabolically stable after being trialed on high dose triheptanoin therapy,” the authors wrote.
Read more about LCFAOD therapies
C16-OH acylcarnitine achieved optimal values during the hospital stay, with plasma levels of 12.4 at 24 hours after birth, which later increased and remained between 3.06 and 4.13 over 8 weeks. Other laboratory testing revealed mild elevations of transaminase and ammonium levels during the first week while ruling out acidosis, rhabdomyolysis, and hypoglycemia at all check-ups.
Further imaging tests reported a Dandy-Walker malformation, severe hydrocephalus, cerebellar vermis hypoplasia, polymicrogyria, and cortex and corpus callosum thinning, leading to a ventriculoperitoneal shunt. Due to clinical and paraclinical stability, the patient was discharged at 9 weeks.
Usually, patients with this type of LCFAOD rarely survive the early neonatal period due to the lack of intrauterine diagnosis of such disorders. This case highlights the importance of screening for congenital malformations on ultrasound since a timely diagnosis could be crucial in preserving a patient’s life.
“Notably our patient’s robust metabolic response occurred while receiving doses of triheptanoin well above the clinical trial doses (7 g/kg vs 4 g/kg) but within limits of [US Food and Drug Administration] approved dosing limits,” the authors explained, highlighting a promising novel option to treat NO-CPT2 deficiency in the future.
Pomerantz DJ, Rush P, Wagner L, Urdahl N, Hight S, Lehman AR. Survival of lethal neonatal CPT-II deficiency with high dose triheptanoin therapy. Mol Genet Metab. Published online March 18, 2022. doi:10.1016/j.ymgme.2022.01.077