Autosomal recessive inheritance

Glucose/galactose malabsotption (GGM) is an intestinal monosaccharide (glucose and galactose) transport deficiency. The disorder manifests itself within the first weeks of life. The severe diarrhea and dehydration are usually fatal unless glucose and galactose are eliminated from the diet. Fiuctose and xylose are absorbed normally. Occurrence in both males and females, familial incidence, in particular in parental consanguinity, indicate autosomal recessive inheritance of... 

Fatal infantile cytochrome c oxidase (CCO) deficiency is characterized by total absence of catalytic activity in skeletal muscle. This often occurs within the context of the Fanconi syndrome, or less commonly in association with a cardiomyopathy. Although the deficiency is global in skeletal muscle, with all fibers affected, only isolated scattered fibers show abnormal aggregations of mitochondria (ragged-red fibers). Multiple affected siblings within one family are frequently encountered and suggest autosomal recessive inheritance. The condition normally proves fatal before the age of six months and is characterized by worsening intractable lactic acidemia. 

Autosomal recessive inheritance Two unaffected people who each carry one copy of the mutated gene for an autosomal recessive disorder (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent. 

Reduced penetrance and variable expressivity are factors that influence the effects of particular genetic changes. These factors usually affect disorders that have an autosomal dominant pattern of inheritance, although they are occasionally seen in disorders with an autosomal recessive inheritance pattern. 

Also see Section II, Chapter 1 Autosomal Recessive Inheritance. 

Primary carnitine deficiency arises from inherited deficiency ofCPT-i or CPT-ii, both of which are rare disorders showing autosomal recessive inheritance. 

A. In autosomal recessive inheritance, the condition is expressed only in persons who have two copies of (ie, are homozygous for) the mutant allele (Figure 13-2). 

Autosomal recessive inheritance is often observed with enzyme deficiencies, where heterozygotes express 50% of normal activity. 

Wilson s disease, an autosomally recessively inherited disorder, is due to a defect in copper metabolism which leads to an accumulation of the element in the liver. A subse-... 

Autosomal recessive-inherited cancer syndromes associated with chromosome fragility or decreased DNA repair predisposes affected individuals to cancer. 

Bernard-Soulier syndrome. Caused by a defect or deficiency in glycoprotein Ib, the receptor for vWF. It is an autosomal recessive inherited disorder. 

Multiple mtDNA deletions in skeletal muscle. Clinical features include adult onset of weakness of the external eye muscles (ophthalmoplegia) and exercise intolerance. Both autosomal dominant and autosomal recessive inheritance can occur, but in most cases it appears to be due to a sporadic deletion or duplication within the mtDNA. 

Phosphofructokinase deficiency (Tarui s disease) is an inborn error of glycogen metabolism characterised by a phosphofructokinase deficiency in the muscles, and associated with abnormal deposition of glycogen in muscle tissues, occasionally with myoglobinuria. The symptoms are similar to those seen in McArdle s disease. Classic Tarui s disease typically presents in childhood with exercise intolerance and anaemia. The fatal infantile variant presents in the first year of life. All reported patients have died by age four years. A late-onset variant manifests itself during later adulthood with progressive limb weakness without myoglobinuria or cramps. It is an autosomal recessive inheritance. Males are slightly more often affected than females. 

Genetic Transmission—59% by autosomal recessive inheritance, thus often appearing in sibs without previous family history remainder sporadic (C8a, M17). 

K8b. Kloepfer, H, W., and Talley, C., Autosomal recessive inheritance of Duchenne-type muscular dystrophy. Ann. Human Genet. 22, 138 (1958). 

Fibrocystic liver diseases, which show an autosomal-recessive inheritance pattern, may hence cause a presinus-... 

Xanthomatosis, an autosomal recessive inherited disorder, was described by A. Abramov, S. Schorr and M. Wolman in 1956. Probably, this rare clinical picture (about 40 cases have been reported to... 

Type 1 is the classic HFE-related form of HC. It has an autosomal recessive inheritance pattern. The gene mutation is localized on chromosome 6, directly next to the A-locus of the HLA system. (426, 427) It was originally... 

Type 2 is the juvenile haemochromatosis. This rare form of iron storage can be differentiated from type 1 by an earlier onset of clinical symptoms. It becomes manifest prior to the age of 30. Both sexes are affected equally. The gene defect is localized on chromosome Iq (A. RoETToetal., 1999). Compared to type 1, cardiomyopathy and hypogonadism are more frequent, the course of disease is more severe and cardiac-induced death is more common. HFE mutations are absent, and there is no association with the HLA system. This form of HC has an autosomal recessive inheritance, (s. tab. 31.17)... 

Wilson s disease is an autosomal recessive inherited disorder of copper metabolism resulting in accumulation of copper in various tissues. Rats raised to have a large accumulation of copper had 80 times greater concentration of MTs in their liver compared to controls (5016pgg vs. 65pgg ). 

Phosphofructokinase deficiency (OMIM 171850) is a rare autosomal recessively inherited disorder. Since red cells contain both M and L submits, mutations affecting the genes coding for these subunits wfil affect enzyme activity. Thus when the PFK deficiency mutation affects only the L subunit, RBCs have only M4 and are PFK deficient. In such cases, there is a mild hemolytic disorder without myopathy. However, when the M subunit is deficient, muscle PFK is virtually absent together with partial PFK deficiency in RBCs, which wfil have only L. Therefore deficiency of the M subunit causes myopathy and a mild hemolytic disorder. 

About 75% of cases of hepatitis in the neonate are idiopathic giant cell hepatitis, a disorder of unknown etiology characterized by cholestatic jaundice. There is a familial trend that may reflect an autosomal recessive inheritance. Jaundice appears withm the first 2 weeks. The child initially appears well and gains weight. The liver and spleen then become enlarged and stools become pale. Serum aminotransferases are usually >400 U/L the prothrombin time is prolonged. Liver biopsy reveals characteristic giant cells with hepatocyte... 

When primary (RIO), the term hypogammaglobulinemia of late onset has been proposed (SIO), as an autosomal recessive inheritance is established in some cases (W15). However discordance in identical twins suggests that the disease can be truly acquired (C20, G13). The incidence is about 1.5 per million living of either sex [equally affected over 10 years of age (Mil)]. 

Demyelination progressive paralysis and dementia death usually occurs within the first decade autosomal recessive inheritance. 

Mental retardation demyelination psychomotor retardation failure to thrive progressive spasticity globoid cells in brain white matter invariably fatal autosomal recessive inheritance. 

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