INBORN  ERRORS

In 1982 the recorded number of human disorders
inherited in simple mendelian fashion/caused by a mutant single gene
amounts to 3,368
[McKusic, V.A., 'Mendelian Inheritance in Man', 6th ed.,Johns Hopkins Univ. Press, Baltimore, 1983].

The clinical effects of the inborn errors of metabolism vary from lethality in utero or in early postnatal life, to very severe handicap [Tay-Sachs disease, Hurler's syndrome, homozzygous talassemia, Lesch-Nyan syndrome, Duchenne muscular dystrophy, Huntington's disease, etc.], to restricted life expectancy, to harmlessness.

For most inborn errors,
therapy is virtually nonexistent, at present.

'Of about 120,000 US babies born each year with a birth defect, 8,000 die during their first year of life......birth defects are the fifth-leading cause of years of potential life lost and contribute substantially to childhood morbidity and long-term disability."
[http://www.cdc.gov/nceh/cddh/BD/bdpghome.htm ]

Most frequent clinical features of inborn diseases
Apathy, ataxia, autistic behaviour [thymine-uracyluria], behavioral disorders, bladder diverticula, blindness [Ehler-Danlos syndrome, tyrosinase-negative albinism, hyperornithinemia type I], cardiomegaly, cardiopathy, cataracts, central nervous system degeneration, cerebellar ataxia, cerebellar degeneration, cerebral degeneration,  cerebral dysfunction, chronic polyneuropathy, cirrhosis, convulsions, cranio-facial dismorfism, craniostenosis, cretinism [hypothyroidism], deafness [Ehler-Danlos syndrome,mitochondrial myopathy, oculo-cranio-somatic-neuromuscular disease, Kearns-Sayre syndrome, Ophtalmoplegia plus, ethanolaminosis], dementia [triose-phosphate isomerase, mucolipidosis IV, familial amaurotic idiocy, neuronal ceroid lipofuscinosis, cerebrotendinous xanthomatosis, adrenoleukodystrophy], developmental disturbances, dysarthria, dwarfism [osteogenesis imperfecta, tryptophanuria, saccharopinuria, cystinosis], face dysmorphism, gigantism, glaucoma, growth retardation, hemyparesis, hemolytic anemia, hepatomegaly, hepatosplenomegaly, hyperacusis, hyperkeratosis, hypertension, impaired intelligence, inguinal hernias,
IQ below 50 [propionic acidemia], ischemic heart disease, jaundice, kernicterus, kyphoscoliosis, lethargy, megaloblastic anemia, mental deficiency [hereditary leucine-sensitive hypoglucosemia, phenylketonuria, sulfituria], mental retardation, microphtalmia, midface deficiency, multiple malformation, myasthenia, myalgia, myoclonus, myopathy, necrotizing encephalopathy, nephrocalcinosis, nephropathy, neurological disorders, neuropsychiatric symptoms, neurosis and psychosis, optic atrophy, osteoporosis, paranoid ideation [mitochondrial myopathy, oculo-cranio-somatic-neuromuscular disease, Kearns-Sayre syndrome, Ophtalmoplegia plus], paraplegia, periodontitis, peripheral neuritis, photosensitivity, premature aging, prominent ears, psychomotor retardation, recurrent infections, schizophrenia-like psychosis, skeletal deformity [abetalipoproteinemia], spasticity, speech disturbance, spinocerebellar degeneration, splenomegalia, urolithiasis, white hair.

The mental retardation, from mild to severe, is present in
a very high proportion of the most frequent 273 inborn diseases: ~ 33 %.

'An estimated 12 of every 1,000 US school children have mental retardation'
[ http://www.cdc.gov/nceh/cddh/fact/mrfs.htm ]

 
Inborn-error   d i s e a s e s   l e a d i n g    to   d e a t h
perinatal death: - alpha-thalassemia, tetrahydrobiopterin deficiency, hyperammonemia type I & type II, citrullinemia, osteogenesis imperfecta, osteopetrosis, Fanconi syndrome, multiple acyl-CoA dehydrogenation deficiency, erythropoietic porphyria, acute intermittent porphyria, coproporphyria, variegate porphyria, Wolman's disease.
death within 5 years: - nephrogenic diabetes insipidus, tyrosinemia type I, Hyperpipecolic acidemia, Maple syrup urine disease,isovaleric acidemia, 3-hydroxyisobutyril CoA hydrolase deficiency, 3-methyl-3-hydroxy-glutaric acidemia, methylmalonic acidemia, ethanolaminosis, homocysteinemia, hyper-b-alaninemia, carnosinuria, a- 1,4-glucosidase deficiency, a- 1,4-glucanbranching enzyme, inactive liver phosphorilase, galactosemia, triose-phosphate isomerase, folic acid deficiency, combined severe immunodeficiency, chronic granulomatous disease, Crigler-Najjar syndrome type I, sialic acid storage disorder, mucolipidosis, gangliosidosis, juvenile gangliosidosis, Tay-Sachs disease, Sandhoff's disease, sphingolipodystrophy, Gaucher's disease, Niemann-Pick disease type C, triglycerid storage disease, adrenoleukodystrophy, Zellweger's syndrome, Menkes' disease.
death at less than 50 years: - glucose-galactose maladsorption, Batter's syndrome, oxalosis type I, Ehler-Danlos syndrome, alaktasia, isolated pyruvate carboxylase deficiency, pyruvate kinase, mitochondrial myopathy, oculo-cranio-somatic-neuromuscular disease, Kearns-Sayre syndrome, Ophtalmoplegia plus, familial hyperuricemic nephropathy, Lesch-Nyhan syndrome, metachromatic leukodystrophy, Krabbe's disease, Fabry's disease, familial amaurotic idiocy, neuronal ceroid lipofuscinosis, cerebrotendinous xanthomatosis.
Sudden Infant Death Syndrome [SIDS] is the leading cause of death of children 1 month to 1 year of age. In the US 5,000 to 6,000 infant deaths are attributed to SIDS each year. Recent findings seems to attribute SIDS to a defect in the SCHAD, short-chain L-3-hydroxylacyl CoA dehydrogenase [inborn error of metabolism][Treacy, E.P. et al., 2000, J. Pediatr., 137(2), 257-259]