Clinical Manifestations

The disorders that are now assigned to the PBD category were described clinically and named before their relation to the peroxisome was understood. This has resulted in a clinical nomenclature that is somewhat confusing, but has been retained because of its long usage. Table 1 lists the main clinical features. Genetic analyses and detailed studies of genotype-phenotype relationships have shown that the PBD can be subdi vided into two groups. The first group includes three disorders that in the past had been considered to be separate clinical entities: the Zellweger syndrome (ZS) (Bowen, et al., 1964; Wilson, et al., 1986; Zellweger, 1987); neonatal adrenoleukodystrophy (NALD) (Ulrich, et al., 1978; Kelley, et al., 1986); and infantile Refsum disease (IRD) (Scotto, et al., 1982). ZS, NALD, and IRD are now considered to represent a clinical continuum, with ZS the most severe, NALD intermediate, and IRD the mildest compared to the other forms, even though in absolute terms it still causes marked disability. "Classical ZS" is a very severe disorder, often leading to death during the first year and psychomotor development is severely compromised and sometimes absent. It is associated with a striking and characteristic defect in neuronal migration (Evrard, et al., 1978). NALD and IRD share many of the features of the features of ZS, but are somewhat milder. Patients live longer; a few have survived to the fourth or fifth decade (Moser, et al., 1995). Clinical distinction between NALD and IRD is difficult. NALD often is associated with abnormalities of the brain white matter, whereas IRD is not. The second PBD group comprises a single disorder, rhizomelic chondrodysplasia punctata (RCDP). RCDP has a distinct phenotype (Spranger, et al., 1971; Braverman, et al., 1997). The major clinical features of RCDP are shortening of the humeri and femurs, which cause the limbs to be short; cataracts, ichthyosis (dry, scaling skin), and severe psychomotor retardation. Radiographs show chondrodysplasia punctata (bony stippling of the cartilages near the joints and spine).

Was this article helpful?

0 0

Post a comment