Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood

Abstract

IntroductionWe describe the natural history of patients with a Zellweger spectrum disorder (ZSD) surviving into adulthood.MethodsRetrospective cohort study in patients with a genetically confirmed ZSD.ResultsAll patients (n = 19; aged 16–35 years) had a follow-up period of 1–24.4 years (mean 16 years). Seven patients had a progressive disease course, while 12 remained clinically stable during follow-up. Disease progression usually manifests in adolescence as a gait disorder, caused by central and/or peripheral nervous system involvement. Nine were capable of living a partly independent life with supported employment. Systematic MRI review revealed T2 hyperintense white matter abnormalities in the hilus of the dentate nucleus and/or peridentate region in nine out of 16 patients. Biochemical analyses in blood showed abnormal peroxisomal biomarkers in all patients in infancy and childhood, whereas in adolescence/adulthood we observed normalization of some metabolites.ConclusionsThe patients described here represent a distinct subgroup within the ZSDs who survive into adulthood. Most remain stable over many years. Disease progression may occur and is mainly due to cerebral and cerebellar white matter abnormalities, and peripheral neuropathy.

Hepatic dysfunction in peroxisomal disorders

“…Liver dysfunction was more extensive in four cases: one had hepatomegaly and three developed liver cirrhosis. Importantly, one of the latter died of liver failure illustrating that liver pathology can prevail [15]. It is remarkable that the latter coincided with extremely high levels of bile acid intermediates in plasma in the first year of life although these dropped markedly by the time of death.…”

“…Impaired bile acid production (see below) may also cause malabsorption of Vitamin K leading to intracranial bleeding [14]. Recently, the clinical and metabolic characteristics of a cohort of 19 patients surviving into adulthood were reported [15]. Again, neurological, vision and hearing impairments that were stable or progressive predominated.…”

Evaluation of C26:0‐lysophosphatidylcholine and C26:0‐carnitine as diagnostic markers for Zellweger spectrum disorders

“…In addition, biochemical abnormalities tend to normalize in aging ZSD patients (Klouwer et al 2016;Berendse et al 2016). As a consequence, diagnosis is often delayed until additional symptoms occur or affected siblings are diagnosed.…”

Synthesis and evaluation of vitamin D receptor-mediated activities of cholesterol and vitamin D metabolites

“…Secondly, we investigated vitamin D metabolite calcitroic acid [13], and cholesterol phase 1 metabolites ursodeoxycholic acid (UDCA), an FDA approved drug against primary biliary cirrhosis [18], cholic acid (CA) a treatment for bile acid synthesis disorders due to enzymatic effects [19], deoxycholic acid (DCA) used for the reduction of fat under the chin [20], chenodeoxycholic acid (CDCA) a treatment against gallstones [21], and hyodeoxycholic acid (HDCA), which is not marketed but has a similar activities to that of CDCA. In addition, phase 2 metabolites were studied such as glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), sulfonolithocholic acid (SLCA), lithocholic acid glucuronides I and II (LCA Gluc I and II).…”