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Neonatal adrenoleukodystrophy/disorders of peroxisomal biogenesis
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Hepatomegaly may be progressive [3]. Levels of transaminase activity in the blood may be elevated [3]. With time, there is little evidence of developmental progress. One patient could smile and roll from supine position at between seven and nine months, but lost these functions shortly thereafter. Another developed some lateral head movement and a smile, which she lost after 12 months [3]. One patient had a cataract [3]. Most patients have died before the second birthday [1, 3, 9]. Mean age of death of the patients was 15 months, while in classical Zellweger syndrome it was 5.7 months. In neonatal ALD, death has occurred as early as four months. A small number of patients have survived to teenage, albeit severely handicapped and dysmorphic, while some patients with infantile Refsum disease have reached adulthood [24, 25]. Impaired hearing and retinopathy have suggested a diagnosis of Usher syndrome. The mental age of patients has seldom exceeded 12 months and some have regressed at three to five years.
Metabolic Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephanie Grünewald, Alex Broomfield, Callum Wilson
Peroxisomal biogenesis disorders (PBD) are a group of disorders that include the phenotypes Zellweger, neonatal ADL and infantile Refsum disease. The most severe form, Zellweger presents at birth with severe hypotonia, hepatomegaly and the characteristic features of a prominent forehead, large anterior fontanelle, mild dysmorphic features (Fig. 14.16) and stippled epiphyseal calcification (Fig. 14.17). The much milder infantile Refsum disease presents with subtle facial features and developmental delay in early childhood. Patients may have autistic features and/or seizures.
Putative adjunct therapies to target mitochondrial dysfunction and oxidative stress in phenylketonuria, lysosomal storage disorders and peroxisomal disorders
Published in Expert Opinion on Orphan Drugs, 2020
Nadia Turton, Tricia Rutherford, Dick Thijssen, Iain P Hargreaves
Peroxisomes are membrane-bound organelles which contain around 50 different enzymes to fulfil their critical roles in a range of metabolic processes including catabolism of polyamines, prostaglandins, purines and eicosanoids, ether phospholipid biosynthesis, fatty acid oxidation, peroxide and ROS metabolism, glyoxylate clearing, and possibly the biosynthesis of isoprenoids [64]. Peroxisomal disorders are heterogeneous metabolic diseases that result from either mutations in genes that encode peroxisomal enzymes (Refsum disease and adrenoleucodystrophy: ALD) [65,66] or occur as the result of defects in peroxisome biogenesis (Zellweger syndrome spectrum disorders and Rhizomelic chondrodysplasia punctate: RCDP) [67]. Peroxisome biogenesis disorders encompass two phenotypic groups: 1. Zellweger syndrome, neonatal ALD, and infantile Refsum disease, which all belong to the Zellweger syndrome spectrum of diseases, and 2. RCDP1 [67].
Use of electron microscopy when screening liver biopsies from neonates and infants: experience from a single tertiary children’s hospital (1991-2017)
Published in Ultrastructural Pathology, 2020
Mikako Warren, Mai Shimura, Eric P. Wartchow, Shoji Yano
EM was used in 24.5% of the cases. EM was less frequently performed on cases where the diagnosis had been already established by pre-biopsy clinical testing and/or microscopic examination. For example, EM was performed on only 9.3% of 204 BA cases and none of 18 cases with choledochal cyst. EM was more frequently performed on cases, where the clinical and microscopic findings are inconclusive. Of these, EM played an important role in 10 cases including glycogen storage disorder (GSD) type 1 with marked accumulation of glycogen dislocating the cell organelles at the periphery of the cells (n = 5), mitochondrial disorder (MD) with mitochondrial pleomorphism and “parking-lot” like crystalloid (paracrystalline) inclusions (n = 2), Niemann-Pick disease (NPD) with numerous myelinosomes in hepatocytes and Kupffer cells (n = 1), Alpha-1 antitrypsin (A1AT) with electron dense deposits within endoplasmic reticulum (n = 1) and infantile Refsum disease (IRD) lacking peroxisomes and with presence of trilamellar inclusions (n = 1).
Ophthalmic manifestations of Heimler syndrome due to PEX6 mutations
Published in Ophthalmic Genetics, 2018
Nutsuchar Wangtiraumnuay, Waleed Abed Alnabi, Mai Tsukikawa, Avrey Thau, Jenina Capasso, Reuven Sharony, Chris F. Inglehearn, Alex V. Levin
The discovery that hypomorphic PEX1 and PEX6 mutations cause Heimler syndrome (2,5) identifies the condition as a peroxisomal disorder. One study suggests that mutations in PEX1 are more common (2) while another found PEX6 mutations to be more common (5). Other peroxisomal disorders include Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and chondrodysplasia punctata. Mutations in PEX1 and PEX6 may also result in a form of Zellweger syndrome, which is characterized by craniofacial abnormalities, neurologic dysfunction, and liver dysfunction (10,11). Ocular manifestations were not specifically described. In other forms of Zellweger syndrome, some of which were not molecularly defined, ocular findings include nystagmus, cloudy corneas, glaucoma, cataract, retinal dystrophy with extinguished ERG, macular intraretinal cystoid spaces, and optic atrophy (10,12–18). Our patients, and those reported by Ratbi and Lima, had a milder form of retinal dystrophy compared to other patients with Zellweger syndrome.