Two Siblings with Phenotypes Mimicking Peroxisomal Disorders but with Discordant Biochemical Findings

Abstract

The authors present a report on two sibling with a nearly identical phenotype mimicking peroxisomal disorder but with totally discordant biochemical findings. In an attempt to confirm the diagnosis of a peroxisomal disorder, plasma levels of very long chain fatty acids (VLCFA) and phytanic acid were determined. In addition, fibroblasts profile of VLCFA and plasmalogen levels were evaluated for Case 2. Pathomorphological examinations represented by lymph node and kidney biopsies as well as postmortem examinations of liver, adrenals and brain were performed in Case 1. The phenotypes of both siblings showed marked resemblance to those observed in children with Zellweger syndrome. The results of biochemical tests performed in Case 1, together with abundant peroxisomes in the liver and the wide spectrum of clinical abnormalities suggest pseudo-Zellweger or Zellweger-like syndromes, but no conclusive data have been found. The plasmalogen level in fibroblasts as well as the fibroblasts profile of VLCFA noted in Case 2 were within the normal range, thus excluding the possibility of a peroxisomal disorder. The striking phenotype resemblance of the siblings mimicking Zellweger, together with discordant biochemical findings, are difficult to explain on the basis of currently available tests.

A new autosomal recessive syndrome with Zellweger‐like manifestations

“…All children have shown the same craniofacial characteristics severe hypotonia, and mental retardation. However macrocephaly was seen in both the patients of Pietrzyk et al [1990] in contrast to the microcephaly seen in our and classical Zellweger patients (Zellweger infants regularly have a small head). Pietrzyk et al [1990] were not able to explain the basis of their disorder at that time, but mitochondrial studies were not obtained.…”

“…In 1990 Pietrzyk et al [1990] described similar Zellweger-like physical findings with discordant biochemical findings in two sibs. Although the first child had elevated phytanic acid and C26 levels, his autopsy showed abundant liver peroxisomes, thus excluding a PBD.…”

“…Furthermore the second child presented with the same clinical picture but results of all peroxisomal tests were normal thus also excluding a single enzyme peroxisomal defect. A comparison of our subjects and those of Pietrzyk et al [1990] to patients with classical ZS is presented in Table I. All children have shown the same craniofacial characteristics severe hypotonia, and mental retardation.…”

Activation of apoptosis and caspase‐3 in zebrafish early gastrulae

“…Furthermore the second child presented with the same clinical picture but results of all peroxisomal tests were normal thus also excluding a single enzyme peroxisomal defect. A comparison of our subjects and those of Pietrzyk et al [1990] to patients with classical ZS is presented in Table I. All children have shown the same craniofacial characteristics severe hypotonia, and mental retardation.…”

“…In 1990 Pietrzyk et al [1990] described similar Zellweger‐like physical findings with discordant biochemical findings in two sibs. Although the first child had elevated phytanic acid and C26 levels, his autopsy showed abundant liver peroxisomes, thus excluding a PBD.…”