A New Variant Mutation in SKIV2L Gene in Case of Trichohepatoenteric Syndrome

Abstract

Trichohepatoenteric syndrome is an autosomal recessive genetic disease with an estimated prevalence of 1:100,000. The mutation of the disease is placed either in SKIV2L or TTC37 genes. The onset of presentation is variable, but symptoms usually start with intractable diarrhea associated with woolly hair abnormality, immune dysfunction, and sometimes hepatic abnormality. This case is of a 10-month-old girl who was born at 37 + 2 weeks due to symmetrical intrauterine growth restriction (IUGR), with a low birth weight (1320 g). It was noticed during her stay in NICU that she had excessive diarrhea on day 8. Gastroenterology suggested starting an extensively-hydrolyzed formula, but no improvement noticed. The multidisciplinary teams decided to order whole-exome sequencing analysis after excluding diarrhea causes. The analysis detected a new variant mutation (c.1297C > T) p. (Arg433Cys). To our knowledge, this is the first time detected in a homozygous state in the SKIV2L gene, as this variant mutation has not been described in any previous literature. Our case was managed mainly by total parenteral nutrition. The patient responded to the treatment appropriately.

Case Report: Novel Compound-Heterozygous Variants of SKIV2L Gene that Cause Trichohepatoenteric Syndrome 2

“…The patient was diagnosed with Dubowitz syndrome in Dyment et al, 2021 [45]. Monies et al, 2015;Lee et al, 2016;Zheng et al, 2016;Bick et al, 2017;Hiejima et al, 2017;Bourgeois et al, 2018;Vardi et al, 2018;Rudilla et al, 2019;Fung et al, 2020;Taher et al, 2020;Dyment et al, 2021;Klee et al, 2021), the incidence of this disease is not significantly different between genders (M:F 17:20) (Table 1). Patients have their onset mostly in the neonatal period, ranging from birth to 0.8 years of age (mean, 29.5 days; median, 17 days).…”

“…In the current study, the patient was fed with an amino-acid formula and parenteral nutrition but subsequently developed complications similar to those associated with TPN. It seems that a small supplement of amino acids can be therapeutic for THES2 patients, but extreme cases might require extraoral administration of an extensively hydrolyzed formula (Taher et al, 2020). THES2 is a severe and potentially fatal disorder; however, only a few patients have been reported to die from THES2 (Fabre et al, 2012;Taher et al, 2020).…”

“…It seems that a small supplement of amino acids can be therapeutic for THES2 patients, but extreme cases might require extraoral administration of an extensively hydrolyzed formula (Taher et al, 2020). THES2 is a severe and potentially fatal disorder; however, only a few patients have been reported to die from THES2 (Fabre et al, 2012;Taher et al, 2020). Nevertheless, most cases lacked long-term follow-up.…”

Expanding the clinical spectrum in trichohepatoenteric syndrome

“…THES has its basis in pathogenic variants in the TTC37 or SKIV2L genes, which encode superkiller (SKI) protein complex (Monies et al, 2015). Fewer than 100 cases have been reported around the world, meaning its prevalence is estimated to be around 1/1,000,000 live births (Taher et al, 2020). Furthermore, regarding the management of the condition, no evidence‐based treatment has been found due to its rarity; instead, nutritional support (long‐term parenteral nutrition if necessary) is principally utilized along with supportive therapy (Fabre et al, 2017), and management of the disease should be individualized according to each patient's needs.…”