Reply to the Letter: “Diagnosis of Peroxisomal Disorders”

Diagnosis of Peroxisomal Disorders

Peroxisomal Disorders: Experience from a Genetic Center in North India

We completely agree with the concern raised by Joob et al that the peroxisomal biogenesis disorders (PBDs) have wide spectrum.[1] The most common disorders found in a Japanese study were X-linked adrenoleukodystrophy (X-ALD) and Zellweger syndrome (ZS).[2] X-ALD is suspected in children usually in the first decade with neuroregression. The magnetic resonance imaging findings suggest leukodystrophy initially involving the dentate nuclei and superior cerebellar peduncles, later involving the whole brain. ZS is a severe form of the disorder presenting in infancy with severe neurologic dysfunction, growth retardation, and chondral calcification or epiphyseal stippling on X-rays.

In the present series, we have described 6 classical cases of PBD (3 ZS, 2 rhizomelic chondrodysplasia punctata, and 1 X-ALD) and highlighted the clinical characteristics and radiological features pointing toward the diagnosis supported by biochemical investigations. Recently, several milder and newer phenotypes associated with the PEX gene are identified with over 14 PEX gene mutations.[3] [4] [5] The diagnosis of milder ZS and single peroxisomal enzyme disorders require high clinical suspicion, extensive biochemical testing, and DNA analysis. The constellation of features includes intellectual disability, epilepsy, cerebellar ataxia, peripheral neuropathy, retinal degeneration, and late-onset leukoencephalopathy in cases with PEX gene mutations.[5] [6] Molecular diagnosis definitely helps in confirming the diagnosis in unusual or atypical cases and helps in the further expansion of the PBD spectrum.

• References

• 1 Joob B, Wiwanitkit V. Diagnosis of peroxisomal disorders. J Pediatr Neurol 2019. doi: 10.1055/s-0039-1692137
• 2 Suzuki Y, Shimozawa N, Yajima S, Inoue K, Orii T, Kondo N. Incidence of peroxisomal disorders in Japan. Jpn J Hum Genet 1996; 41 (01) 167-175
• 3 Braverman NE, Raymond GV, Rizzo WB. , et al. Peroxisome biogenesis disorders in the Zellweger spectrum: an overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab 2016; 117 (03) 313-321
• 4 Waterham HR, Ebberink MS. Genetics and molecular basis of human peroxisome biogenesis disorders. Biochim Biophys Acta 2012; 1822 (09) 1430-1441
• 5 Alshenaifi J, Ewida N, Anazi S. , et al. The many faces of peroxisomal disorders: lessons from a large Arab cohort. Clin Genet 2019; 95 (02) 310-319
• 6 Zhang C, Zhan FX, Tian WT. , et al. Ataxia with novel compound heterozygous PEX10 mutations and a literature review of PEX10-related peroxisome biogenesis disorders. Clin Neurol Neurosurg 2019; 177: 92-96