Cerebrohepatorenal syndrome (Zellweger syndrome; 214100*)

Peroxin-1

Biochemical profile: Decreased dihydroxyacetone phosphate acyltransferase and plasmalogen; elevated very long-chain fatty acids, phytanic acid, pipecolate, iron, and total iron-binding capacity

Clinical features: Growth failure, large fontanelles, macrocephaly, turribrachycephaly, dysmorphic facies, cataracts, nystagmus, congenital heart disease, hepatomegaly, biliary dysgenesis, hypospadias, renal cysts, hypotonia, brain malformation

Treatment:

Peroxin-2

Peroxin-3

Peroxin-5

Peroxin-6

Peroxin-12

Peroxin-14

Peroxin-26

Neonatal adrenoleukodystrophy (202370*)

Peroxin-1

Biochemical profile: Elevated very long-chain fatty acids

Clinical features: Dolichocephaly, dysmorphic facies, cataracts, hyperpigmentation, seizures, developmental delay, adrenal insufficiency

Treatment: Symptomatic, no specific treatment

Peroxin-5

Peroxin-10

Peroxin-13

Peroxin-26

Infantile Refsum disease (266510*)

Peroxin-1

Biochemical profile: Elevated plasma phytanic acid, cholesterol, very long-chain fatty acids, dihydroxycholestanoic acid, trihydroxycholestanoic acid, and pipecolic acid

Clinical features: Growth and developmental delay, peripheral neuropathy, hypotonia, deafness, facial dysmorphism, retinopathy, osteoporosis, steatorrhea, episodic bleeding, hepatomegaly

Treatment: Symptomatic, no specific treatment

Peroxin-2

Peroxin-26

Rhizomelic chondrodysplasia punctata

Biochemical profile: In type 1 (215100*), plasmalogen deficiency, elevated plasma phytanic acid and unprocessed 3-oxoacyl CoA thiolase, acyl-CoA dihydroxyacetonephosphate acyltransferase deficiency

In type 2 (222765*), normal plasmalogen, phytanic acid, alkyl dihydroxyacetonephosphate synthase, and peroxisomal thiolase; dihydroacetonephosphate acyltransferase deficiency

In type 3 (600121*), abnormal peroxisomes, alkyl dihydroxyacetonephosphate synthase deficiency

Clinical features: Dwarfism with rhizomelic limb shortening, punctuate epiphyseal calcification, and metaphyseal splaying; severe growth and developmental delay; microcephaly; midface hypoplasia; micrognathia; sensorineural deafness; cataracts; cleft palate; ichthyosis; respiratory difficulties; kyphoscoliosis; vertebral clefts; spasticity; cortical atrophy; seizures; death before 2 years

Treatment: Symptomatic, no specific treatment

Type 1 (215100*)

Peroxin-7

Type 2 (222765*)

Dihydroxyacetonephosphate acyltransferase

Type 3 (600121*)

Alkyldihydroxyacetonephosphate synthase

Hyperpipecolicacidemia (239400*)

Pipecolate oxidase

Biochemical profile: Elevated plasma pipecolate, mild generalized aminoaciduria

Clinical features: Hepatomegaly, demyelination, central nervous system degeneration, severe intellectual disability and developmental delay, retinopathy

Treatment: Symptomatic, no specific treatment

X-linked adrenoleukodystrophy (300100*)

ATP-binding cassette transporter 1

Biochemical profile: Elevated plasma very long-chain fatty acids, peroxisomal lignoceroyl-CoA ligase deficiency

Clinical features: Hyperpigmentation, blindness, cognitive hearing loss, spastic paraplegia, impotence, sphincter disturbance, ataxia, dysarthria, adrenal insufficiency, hypogonadism, pontine and cerebellar atrophy

Treatment: Adrenal hormone replacement, bone marrow transplantation

4:1 mixture of glyceryl trioleate and glycerol trierucate (Lorenzo’s oil) apparently of no clinical benefit once the disease manifests but may slow progression if used prior to symptom onset

Some success in current gene therapy trials

Acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy; 264470*)

Straight-chain peroxisomal acyl-CoA oxidase

Biochemical profile: Elevated plasma very long-chain fatty acids; normal peroxisomal phytanate, pipecolate, dihydroxycholestanoic acid, and trihydroxycholestanoic acid

Clinical features: Neonatal hypotonia, developmental delay, sensorineural deafness, retinopathy, no dysmorphic features, leukodystrophy at age 2 to 3 years

Treatment: Not established

D-Bifunctional protein deficiency (261515*)

D-bifunctional enzyme

Biochemical profile: Elevated serum very long-chain fatty acids and pipecolate, elevated trihydroxycholestanoic acid in duodenal aspirate, peroxisomal 3-oxoacyl-CoA thiolase defect

Clinical features: Hypotonia, exaggerated startle reflex, facial diplegia, seizures, high-pitched and weak cry, developmental delay, myopathic facies, high-arched palate, abducted limbs, ventricular heart disease

Treatment: Not established

2-Methylacyl-CoA racemase deficiency (614307*)

2-Methylacyl-CoA racemase

Biochemical profile: Elevated plasma pristanic acid

Clinical features: Adult-onset sensorimotor neuropathy, retinopathy

Treatment: Not established

Primary oxaluria

Biochemical profile: Elevated urinary oxalate excretion, glycolic aciduria

Clinical features: Calcium oxalate urolithiasis, nephrocalcinosis, renal failure, heart block, peripheral vascular insufficiency, arterial occlusion, intermittent claudication, optic neuropathy, fractures, death during childhood or early adulthood

Type 2 milder than type 1

Treatment: Hepatorenal transplantation

Hyperoxaluria type 1 (259900*)

Peroxisomal alanine-glyoxylate aminotransferase

Hyperoxaluria type 2 (260000*)

D-Glycerate dehydrogenase glyoxylate reductase

Refsum disease (266500*)

Phytanoyl-CoA hydroxylase

Biochemical profile: Elevated plasma and tissue phytanic acid

Clinical features: Retinitis pigmentosa, ataxia, ptosis, miosis, peripheral neuropathy, anosmia, heart failure, deafness, ichthyosis, short 4th metacarpal

Treatment: Low phytanic acid diet, plasmapheresis

Peroxin-7

Glutaric aciduria type 3 (231690*)

Peroxisomal glutaryl CoA oxidase

Biochemical profile: Glutaric aciduria exacerbated by lysine loading

Clinical features: Failure to thrive, postprandial vomiting

Treatment:

Mevalonic aciduria (610377*)

See table Branched-Chain Amino Acid Metabolism Disorders

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Acatalasemia (115500*)

Catalase

Biochemical profile:

Clinical features: Ulcerating oral lesions in Japanese patients but not in Swiss patients

Treatment: Symptomatic, no specific treatment