Hereditary syndrome

HIPOURICEMIA, HYPERCALCIURIA AND DECREASED BONE DENSITY, A NEV HEREDITARY SYNDROME... 

The cause of the neurologic symptomatology is obscure. The co-occurrence of ataxia and atypical pigmentary retinitis is a feature in several other hereditary syndromes, so that a common pathogenesis is likely for both symptoms. Gai-TONDE (1963) has emphasized the importance of lipoproteins for the metabolism of the nervous system, but the causal relation of a-jS-lipoproteinemia and ataxic disturbance has not yet been elucidated. It is possible that there is a common factor essential for the normal structure and function of the nerve cell on one hand, and the production of j8-lipoproteins on the other (Salt et al. 1960), but it appears more likely that the lack of j8-lipoprotein formation actually represents the central lesion. 

Mutations in human Kv-channel genes have been detected that are associated with hereditary diseases ranging from heart arrythmia (long QT-syndrome) and deafness to epilepsy and ataxia (see Table 2). Typically, many Kv-channel related channelopathies are correlated with a mutant phenotype that is episodic in nature and appears as a dominant hereditary trait. 

Fatal hereditary disorder that typically presents in the neonatal period. Clinical features include an array of hepatic, renal and neurological dysfunctions. Patients with Zellweger syndrome rarely survive the first year of life. The disease is caused by mutations in the Pex proteins leading to an defective import of peroxisomal matrix proteins and consequently to a loss of most peroxisomal metabolic pathways. 

These disorders are all acquired conditions with no evidence of an hereditary basis. Most of them involve inflammation of the skeletal muscle itself (myositis) (Figure 17), though this may sometimes occur because of initial targeting of the muscle vasculature or connective tissue. Many instances of myositis are classed as idiopathic disorders, in that the precise mechanisms of muscle degeneration are not known, but is widely accepted that these syndromes are associated with abnormal function of the immune system. The syndromes of polymyositis (PM) and derma-... 

Data in part from Ackerman NJ, Clapham DE Ion channels— basic science and clinical disease. N Engl J Med 1997,-336 1575. Other channelopathies include the long QT syndrome (MIM 192500) pseudoaldosteronism (Liddle syndrome, MIM 177200) persistent hyperinsulinemic hypoglycemia of infancy (MIM 601820) hereditary X-linked recessive type II nephrolithiasis of infancy (Dent syndrome, MIM 300009) and generalized myotonia, recessive (Becker disease, MIM 255700). The term "myotonia" signifies any condition in which muscles do not relax after contraction. 

Alport s syndrome A hereditary disease that affects kidney function and can also cause hearing and vision disorders. 

Hereditary triose phosphate isomerase (TPI) deficiency is an autosomal recessive disorder that has the most severe clinical manifestations of the erythroenzy-mopathies, including hemolytic anemia, neurological dysfunction, sudden cardiac death, and increased susceptibility to infection. Since the first description by Schneider et al. (S10), more than 25 unrelated families have been reported (Fll). Cases of decreased TPI activities associated with cat cry syndrome and pancytopenia were reported, whereas the correlation between TPI deficiency and these disorders was not clear. Although the degree of anemia is variable, most patients require blood transfusions. Neurological involvement, such as paraparesis, weakness, and hypotonia, is progressive in most cases. No specific therapy is available for the neuropathic manifestations of the disease, and most severely affected children fail to survive beyond the age of 5 years. 

Pyrimidine 5 -nucleotidase (P5N) deficiency appears to be the third most common cause of hereditary nonspherocytic hemolytic anemia after G6PD and PK deficiencies. To date, more than 42 cases have been reported worldwide (FI 1) since the first report by Valentine et al. (V4). This syndrome is characterized by hemolytic anemia, pronounced basophilic stippling of red blood cells (Fig. 6), and a... 

L-ferritin Iron storage Hereditary hyperferri tinaemia -ca ta ract syndrome (Girelli et ah, 1995 Aguilar-Martinez et ah, 1996 Mumford et ah, 1998 Martin et ah, 1998)... 

Fetal alcohol syndrome (FAS) is a pattern of birth defects caused by maternal consumption of ethanol during pregnancy. It is recognized by growth deficiency, a characteristic set of craniofacial features and neurodevelopmental abnormalities leading to cognitive and behavioral deficits [85]. FAS is considered to be the most common non-hereditary cause of mental retardation. 

Homocystinuria can be treated in some cases by the administration of pyridoxine (vitamin Bs), which is a cofactor for the cystathionine synthase reaction. Some patients respond to the administration of pharmacological doses of pyridoxine (25-100 mg daily) with a reduction of plasma homocysteine and methionine. Pyridoxine responsiveness appears to be hereditary, with sibs tending to show a concordant pattern and a milder clinical syndrome. Pyridoxine sensitivity can be documented by enzyme assay in skin fibroblasts. The precise biochemical mechanism of the pyridoxine effect is not well understood but it may not reflect a mutation resulting in diminished affinity of the enzyme for cofactor, because even high concentrations of pyridoxal phosphate do not restore mutant enzyme activity to a control level. 

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