MedGen

The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX16 gene have cells of complementation group 9 (CG9, equivalent to CGD). For information on the history of PBD complementation groups, see 214100. [from OMIM]

Patients with deficiency of C8 suffer from recurrent neisserial infections, predominantly with meningococcus infection of rare serotypes. Most such patients are discovered among those having their first episode of meningitis at ages older than 10 years (Ross and Densen, 1984). Two types of inherited C8 deficiency have been reported in humans: type I (613790), in which only C8 alpha (C8A, 120950) and C8 gamma (C8G; 120930) are deficient, and type II, in which only C8 beta is deficient (Marcus et al., 1982; Tedesco et al., 1983). The 2 types are clinically indistinguishable (Ross and Densen, 1984). [from OMIM]

Autosomal recessive agammaglobulinemia-8B (AGM8B) is characterized by onset of recurrent infections in early childhood. Laboratory studies of affected individuals show decreased circulating immunoglobulins and decreased peripheral B cells. More variable features may include dysmorphic facies and subtle abnormalities of other immune cells, such as T cells. One patient who developed childhood B-cell acute lymphocytic leukemia (B-ALL) has been described (summary by Ben-Ali et al., 2017). [from OMIM]

Four phenotypes comprise the RRM2B mitochondrial DNA maintenance defects (RRM2B-MDMDs): RRM2B encephalomyopathic MDMD, the most severe phenotype, usually manifesting shortly after birth as hypotonia, poor feeding, and faltering growth requiring hospitalization. Subsequent assessments are likely to reveal multisystem involvement including sensorineural hearing loss, renal tubulopathy, and respiratory failure. Autosomal dominant progressive external ophthalmoplegia (adPEO), typically adult onset; other manifestations can include ptosis, bulbar dysfunction, fatigue, and muscle weakness. RRM2B autosomal recessive progressive external ophthalmoplegia (arPEO), a typically childhood-onset predominantly myopathic phenotype of PEO, ptosis, proximal muscle weakness, and bulbar dysfunction. RRM2B mitochondrial neurogastrointestinal encephalopathy (MNGIE)-like, characterized by progressive ptosis, ophthalmoplegia, gastrointestinal dysmotility, cachexia, and peripheral neuropathy. To date, 78 individuals from 52 families with a molecularly confirmed RRM2B-MDMD have been reported. [from GeneReviews]