Disease Catalogue

Acatalasemia Single Enzyme Deficiency Deficiency in catalase activity. Two major variants of symptoms:

a) Japanese variant (oral ulcerations and gangrene).

b) Swiss variant (asymptomatic).
Acyl-CoA oxidase deficiency (Pseudoneonatal adrenoleukodystrophy) Single Enzyme Deficiency Deficiency for acyl-CoA oxidase 1 (ACOX1). Symptoms: abnormal presence of VLCFAs, generalized hypotonia, severe delayed motor development and sensory deafness.
Adult-onset sensory motor neuropathy Single Enzyme Deficiency Also called alpha-methylacyl-CoA racemase deficiency. Symptoms: reported in three patients: high levels of pristanic acid and biliar acid C27 in plasma, pigmentary retinopathy, epileptic seizures.
Amyotrophic lateral sclerosis, ALS1 Single Enzyme Deficiency From 15 to 20% of cases of ALS type 1 are associated with mutations in the superoxide dismutase-1 gene. Symptoms: rapidly progressive loss of motor function with predominantly lower motor neuron manifestations and a course of less than 5 years.
Bifunctional protein deficiency Single Enzyme Deficiency The clinical manifestations mimic those of the Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease continuum associated with PDB.
Contiguous ABCD1/DXS1375E deletion syndrome Single Enzyme Deficiency Symptoms: profound neonatal hypotonia, subsequent failure to thrive, and cholestatic liver disease.
Glomerulosclerosis Single Enzyme Deficiency In mice, main symptom is nephrotic syndrome at early age. No patients identified.
Glutaric aciduria type III Single Enzyme Deficiency Patients lacking activity of peroxisomal glutaryl-CoA oxidase can develop failure to thrive, homozygous beta thalassemia, gastroenteritis and hyperthyroidism.
Hyperoxaluria type I Single Enzyme Deficiency Symptoms: kidney failure due to elevated levels of oxalate, the main component of kidney stones.
Infantile Refsum disease Peroxisome Biogenesis Disorder It has characteristics in common with both Zellweger syndrome and neonatal adrenoleukodystrophy, but milder pathology and abnormalities. Symptoms: severe physical, sensory and developmental disabilities. However, IDR children usually attain some degree of motor, cognitive and comunication skills.
Malonic aciduria Single Enzyme Deficiency Increased high levels of malonate. Symptoms: developmental delay, vomiting, seizures, cardiomyopathy and hypoglycemia.
Mental retardation X-linked 63, MRX63 Single Enzyme Deficiency Symptoms depending on sex.

a) Affected males: nonspecific, nonprogressive mental retardation ranging from severe to moderate, without seizures.

b) Carrier females: highly variable cognitive capacities, ranging from moderate mental retardation to normal intelligence.
Mulibrey nanism Single Enzyme Deficiency Mulibrey nanism = Muscle-liver-brain-eye nanism. Autosomal recessive. Symptoms: severe growth failure of perinatal onset, dysmorphic features, pericardial constriction, and hepatomegaly.
Neonatal adrenoleukodystrophy Peroxisome Biogenesis Disorder Neonatal adrenoleukodystrophy has many characteristics in common with Zellweger syndrome, but dysmorphic facial and skeletal abnormalities are less pronounced, and there is no calcification of cartilage. Symptoms: adrenal atrophy, degenerative changes of the white matter, dolicocephaly, prominent and high forehead, high level of pipecolic acid in serum. Men and women are equally affected. Levels of VLCFA in parents are normal.
Refsum disease Single Enzyme Deficiency Characterised by an accumulation of phytanic acid in plasma and tissues. Symptoms: neurodegeneration, failure of muscle coordination, retinitis pigmentosa and bone and skin changes.
Rhizomelic chondrodysplasia punctata type 1 (RCDP1 ) Peroxisome Biogenesis Disorder Genetically heterogeneous group of bone dysplasias. Symptoms: disproportionally short stature primally affecting the proximal parts of extremities, typical facial appearance, congenital contractures and severe mental retardation with spasticity.
Rhizomelic chondrodysplasia punctata type 2 (RCDP2) Single Enzyme Deficiency Defects that involve alkyl DHAP synthase and alkyl DHAP transferase. Symptoms: Deficient plasmalogen levels in all tissues, including erythrocytes. Symptoms are associated with the clinical manifestations of rhizomelic chondrodysplasia punctata.
Rhizomelic chondrodysplasia punctata type 3 (RCDP3) Single Enzyme Deficiency Defects that involve alkyl DHAP synthase and alkyl DHAP transferase. Symptoms: associated with the clinical manifestations of rhizomelic chondrodysplasia punctata.
Sjogren-Larsson syndrome Single Enzyme Deficiency Disorder related to phytanic acid metabolism. Symptoms: similar to a neurological disorder with spastic quadriplegia. Skin changes similar to those of congenital ichthyosiform erythroderma. Considerable variations in severity have been described.
X-linked adrenoleukodystrophy Single Enzyme Deficiency Severe X-linked demyelinating disorder due to mutations in the ALD protein, presumably implicated in the transport of VLCFAs into the peroxisome. Prevalence is about one in 20000 males. Six categories of symptoms:

1) Childhood cerebral ALD (CCALD): aprox. 30% of the patients. Up to the point of onset (5 to 10 years), development is normal. The most common initial symptoms are difficulties in school, behavioral disturbances, impaired vision or hearing. After initial neurological symptoms appear, the health of the patients deteriorates rapidly, and demyelination leads to death.

2) Adolescent cerebral (ALD): the symptoms and progression of the disease are similar to those of childhood cerebral ALD.

3) Adult cerebral (ALD): relatively rare. The age of onset varies from the twenties to the fifties. The symptoms are similar to those of schizophrenia with dementia. Rapid progression of the disorder.

4) Adrenomyeloneuropathy (AMN): aprox. 40-45% of the patients. The most common ALD phenotype. Initial symptoms are stiffness/clumsiness in the legs, weight loss, attacks of nausea, and generalized weakness. The disease progresses slowly.

5) Symptomatic heterozygotes: 20% of heterozygous women do show some symptoms of AMN. The symptoms can range from very mild to very severe, although heterozygote women rarely have impaired adrenal function or brain involvement.

6) Adrenal insufficiency-only: aprox. 10% of the patients. The symptoms ressemble Addison disease.
Xanthinuria Single Enzyme Deficiency Excretion of very large amounts of xanthine in the urine. The main symptom is the tendency to form xanthine stones. Two distinct but clinically similar forms:

Type I: isolated deficiency of xanthine dehydrogenase

Type II: dual deficiency of xanthine dehydrogenase and aldehyde oxidase.
Zellweger syndrome Peroxisome Biogenesis Disorder Autosomal recessive lethal disorder caused by mutations in different genes involved in peroxisome biogenesis. Symptoms: organs affected are liver, kidney and brain of infants. Polymicrogyria, enlarged liver, high levels of iron and copper in blood, and vision disturbances are among the major clinical manifestations.