There are two types of peroxisomal disorders:
Peroxisomes are intracellular organelles that contain enzymes for the ?-oxidation. These enzymes overlap in their function to those in the mitochondria, with the exception that mitochondria have no enzymes, the very long chain fatty acids (VLCFA) with 20-26 can metabolize hydrocarbons. Therefore Peroxisomenstörungen manifest by an increase in VLCFA levels (with the exception of rhizomelischen chondrodysplasia). Although the VLCFA levels are in this disorder in the screening of benefits, other assays are needed such. B. Serum levels of Phytan-, Pristan- and Pipecolsäuren, erythrocyte plasma lodges mirror. For more information about other diseases that affect the fatty acid metabolism, see Overview of fatty acid and glycerol metabolic disorders. See also Procedure in a patient with suspected congenital metabolic disorder and investigation for suspected inherited metabolic disorders. There are 2 types of peroxisomal disorders: Those with defective Peroxisomenbildung those with defects in single peroxisomal enzymes X-linked adrenoleukodystrophy is the most common peroxisomal disorder (incidence 1 / 17,000 live births); all others are transmitted as an autosomal recessive trait, and have a combined incidence of 1 / 50,000 births. For more information, see table. Peroxisome biogenesis and disturbances in the metabolism of very long chain fatty acids disease (OMIM number) Defective proteins or enzymes defective gene or genes (chromosomal location) Comments cerebro-hepato-renal syndrome (Zellweger syndrome; 214,100) Peroxin-1 EX1 (7q21-q22 ) * Biochemical profile: Decreased Dihydroxyacetonphosphatacyltransferase and plasmalogenes; increased very long chain fatty acids, phytanic acid, pipecolate, iron and total iron binding capacity Clinical features: growth disorder, large fontanelle, macrocephaly, Turribrachyzephalie, facial dysmorphism, cataracts, nystagmus, congenital heart defects, hepatomegaly, Gallenwegsdysgenesie, hypospadias, renal cysts, hypotension, brain malformation treatment: There is no effective therapy. Ether lipids, reduction of phytanic acid in the diet and docosahexaenoic acid möglichlicherweise Peroxin-2 PEX2 (8q21.1) * Peroxin-3 PEX3 (6q23-q24) * Peroxin-5 PEX5 (12p13.3) * Peroxin-6 PEX6 (6p21.1) * Peroxin-PEX12 12 (17) * Peroxin-14 Pex14 (1p36.2) * Peroxin-26 PEX26 (22q11,21) * Neonatal Adrenoleukodystrophy (202,370) Peroxin PEX1-1 (7q21-q22) * biochemical profile: increased very long chain fatty acids Clinical features: dolichocephaly, facial dysmorphism, cataracts, hyperpigmentation, seizures, developmental delay, adrenal insufficiency treatment: Similar to Zellweger syndrome Peroxin-5 PEX5 (12p13.3) * Peroxin-10 PEX10 (1) * 13 Peroxin-PEX13 (2P15) * Peroxin-26 PEX26 (22q11,21) * Infantile Refsum Disease (266510) Peroxin PEX1-1 (7q21-q22) * biochemical profile: Elevated phytanic acid, cholesterol, very long chain fatty acids, Dihydroxycholestansäure, Trihydroxycholestanoic acid and pipecolic acid in blood Clinical features: growth retardation, peripheral neuropathy, hypotension, deafness, facial dysmorphism, retinopathy, osteoporosis, steatorrhea, episodic bleeding, hepatomegaly treatment: Similarly w ie at Zellweger syndrome Peroxin-2 PEX2 (8q21.1) * Peroxin-26 PEX26 (22q11,21) * Rhizomelische chondrodysplasia punctata biochemical profile: In Type 1, plasmalogen deficiency, elevated phytanic acid in the blood and unprocessed 3-oxoacyl-CoA thiolase , acyl-CoA Dihydroxyacetonphosphatacyltransferase deficiency in type 2 normal plasmalogen, phytanic acid, and Alkyldihydroxyacetonphosphatsynthase Peroxisomenthiolase; Dihydroacetonephosphatacyltransferase deficiency in type 3 conspicuous peroxisomes, alkyl Dihydroxyacetonphosphatsynthase deficiency Clinical features: dwarfism with shortening of the extremities rhizomelic interrupted epiphyseal and metaphyseal calcification spreading, heavy growth and developmental delays, microcephaly, midface; Micrognathia; Hearing loss; Cataract; Cleft palate; ichthyosis; Difficulty breathing; Kyphoscoliose; Vertebral column; spasticity; cortical atrophy; Seizures, death before the age of 2 years of treatment: As with Zellweger syndrome type 1 (215100) peroxin-7 PEX7 (6q22-q24) * Type 2 (222765) dihydroxyacetone phosphate acyltransferase GNPAT (1) * Type 3 (600121) Alkyldihydroxyacetonephosphat synthase AGPS (2q31) * Hyperpipecolinazidämie (239400) Pipecolatoxidase Biochemical profile: Increased pipecolate in the blood, mild generalized aminoaciduria Clinical features: hepatomegaly, demyelination, CNS degeneration, severe mental retardation and developmental delay, retinopathy treatment: reduced intake of very long chain fatty acids X-linked leukodystrophy (300100) ATP-binding cassette transporter 1 ABCD1 (Xq28) * Biochemical profile: Very long chain fatty acids in the blood increases, peroxisomal lignoceroyl-CoA ligase deficiency Clinical characteristics: hyperpigmentation, blindness, cognitive hearing loss, spastic paraplegia impotence, sphincter defect, ataxia, dysarthria, adrenal insufficiency, hypogonadism, pontine and cerebellar atrophy treatment: adrenal hormone replacement therapy, bone marrow transplantation A 4: 1 mixture of glycerin and glyceryl trierucate (Lorenzo oil) is apparently without clinical benefit acyl-CoA oxidase 1 deficiency (pseudoneonatale adrenoleukodystrophy; 264 470) Straight-chain peroxisomal acyl-CoA oxidase ACOX (17q25) * Biochemical Profile: Very long chain fatty acids in the blood increases; normal peroxisome Phytanat, pipecolate, Dihydroxycholestanoic acid and acid Trihydroxycholestanoic Clinical features: neonatal hypotonia, developmental delay, hearing loss, retinopathy, no facial dysmorphism, leukodystrophy aged 2-3 years. Treatment: Not determined D-bifunctional protein deficiency (261,515) D-bifunctional enzyme HSD17B4 (5q2) * Biochemical Profile: In the blood increased very long chain fatty acids and pipecolate, increased trihydroxycholestanoic acid in Duodenalaspirat, disorder of peroxisomal 3-oxoacyl-CoA thiolase Clinical features: hypotension, exaggerated startle response, Gesichtsdiplegie, seizures, shrill and faint cries, developmental delay, myopathic face, high-arched palate, splayed limbs, ventricular heart disease treatment: Not specified 2-methylacyl-CoA racemase deficiency 2-methylacyl-CoA racemase AMACR (5p13.2-Q11.1) * Biochemical Profile: Increased pristanic in blood Clinical features: adult onset with sensorimotor neuropathy, retinopathy treatment: Not Set Primary oxaluria Biochemical Profile: Increased oxalate in the urine, Glykolazidurie Clinical features: calcium oxalate Urolithiase , nephrocalcinosis, kidney failure, heart block, peripheral vascular insufficiency, arterial occlusion, claudication, optic neuropathy, fractures, death during childhood or early adulthood type 2 weaker than type 1 treatment: hepatorenal transplantation hyperoxaluria type 1 (259900) Peroxisomal Alaninglyoxylate aminotransferase AGXT (2q36-q37) * hyperoxaluria type 2 (260000) D-glycerates dehydrogenase glyoxylate reductase GRHPR (9cen) * Refsum disease (266500) phytanoyl-CoA hydroxylase PAHX (10pter-p11.2) * Biochemical profile: Increased phytanic in blood and tissue Clinical features: retinitis pigmentosa, ataxia, ptosis, miosis, peripheral neuropathy, anosmia, heart failure, deafness, ichthyosis, short fourth metacarpals treatment: reduction of phytanic in the diet, plasmapheresis Peorxin-7 PEX7 (6q22-q24) * glutaric aciduria type 3 (231,690) Peroxisomal glutaryl-CoA oxidase biochemical profile: Glutarzidurie by lysine load exacerbated Clinical features: failure to thrive, postprandial vomiting treatment: Not determined Mevalonsäureazidurie See Table metabolic disorders of branched chain amino acids – – Acatalasemia (115500) Catalase CAT (11p13) * Biochemical Profile: The tissue can not foaming bring Clinical features hydrogen peroxide: Ulcerative lesions of the mouth in Japanese, but not in patients in Switzerland Treatment: symptomatically The gene was identified, and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Zellweger syndrome (ZS), neonatal adrenoleukodystrophy and infantile Refsum disease (IRD) These three terms describe the clinical course of very pronounced (ZS) to less bad (IRD). The responsible gene defect occurs in one of at least 11 genes against which are involved in the formation of peroxisomes or Proteineinschleusung (PEX gene family). Manifestations include a dysmorphia of the face, CNS malformations, demyelination, neonatal convulsions, hypotension, hepatomegaly, cystic kidneys, short extremities with stippled epiphyses (chondrodysplasia punctata), cataract, retinopathy, hearing impairments, psychomotor retardation and a peripheral neuropathy. The diagnosis is made because of the increased blood levels of VLCFA, phytanic, bile acid degradation products and pipecolic acid. An experimental treatment with docosahexanoic acid (DHA levels are reduced in patients with a disorder of Peroxisomenbildung) seems to be promising success. Chondrodysplasia punctata Rhizomelische The defect in the peroxisomal biogenesis is caused by a gene mutation PEX7 and is characterized by skeletal changes as midface, very short proximal members, frontal protuberances, narrow nostrils, cataracts, ichthyosis and a pronounced psychomotor retardation. Also vertebral columns are often seen. The diagnosis of Chrondodysplasia punctata rhizomelic is provided due to X-rays, increasing the phytanic and low erythrocyte plasma lodges mirror. The VLCFA levels are normal. There is no effective therapy for rhizomelische chondrodysplasia punctata X-linked leukodystrophy This disorder is caused by a deficiency of the peroxisomal membrane transporter ALDP, which is encoded by the gene ABCD1-. The cerebral form affects 40% of patients. The onset of the disease is between 4 and 8 years, and the symptoms of attention deficit disorder go through with time in severe behavioral disorders, dementia, impaired vision and hearing loss and motor deficits that cause complete obstruction and 2-3 years after diagnosis to death to lead. A less severe form of juvenile and adult was also described. Approximately 45% of patients suffer from the milder form, adrenomyeloneuropathy (AMN) is called; the onset of the disease is between 20 and 40 years with a progressive paraparesis and disorders of the sphincter function and sexuality. About a third of these patients developed cerebral symptoms. Patients may develop adrenal insufficiency in all forms; about 15% have an isolated Addison’s disease without neurological involvement. The diagnosis of X-linked adrenoleukodystrophy is confirmed with an isolated increase VLCFA. A bone marrow or stem cell transplantation may stabilize symptoms in selected cases. Patients with adrenal insufficiency have received steroid therapy. A dietary substitution with a 4: 1 mixture of glyceryl and Glyceryltrierucat (Lorenzo-oil) can normalize the VLCFA levels and help some patients. Corresponding studies are ongoing. Classical Refsum syndrome A genetic deficiency of a single peroxisomal enzyme, phytanoyl-CoA hydroxylase, which catalyzes the metabolism of the phytanic acid (a common vegetable ingredient), leads to the accumulation of phytanic acid. The clinical manifestations include a progressive peripheral neuropathy, a visual blurring due to retinitis pigmentosa, hearing loss, anosmia, cardiomyopathy and conduction disturbances and ichthyosis. The disease begins in the third decade of life. The diagnosis of Refsum syndrome is confirmed by the increase of the phytanic acid in the serum and the lowered Pristansäurespiegel (the increase of the phytanic acid is in some other Peroxisomenstörungen accompanied by an increase in the pristanic). The treatment of Refsum disease is a dietary restriction of phytanic acid (<10 mg / day), which is very effective in preventing or delaying the symptoms if started before the onset of symptoms.