Four new cases of stomatin‐deficient hereditary stomatocytosis syndrome: association of the stomatin‐deficient cryohydrocytosis variant with neurological dysfunction

• Published in: British journal of haematology Vol. 125; no. 6; pp. 796 - 803
• Main Authors: Fricke, Britta, Jarvis, Helen G., Reid, Cecil D. L., Aguilar‐Martinez, Patricia, Robert, A., Quittet, P., Chetty, Margaret, Pizzey, Arnold, Cynober, Thérèse, Lande, William F., Mentzer, William C., Düring, Monika, Winter, Stuart, Delaunay, Jean, Stewart, Gordon W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: Adult; Anemia, Hemolytic, Congenital Nonspherocytic - complications; Anemias. Hemoglobinopathies; Biological and medical sciences; Blood Proteins - deficiency; Blotting, Western - methods; cataracts; congenital haemolytic anaemia; Diseases of red blood cells; Erythrocyte Membrane - chemistry; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hematologic and hematopoietic diseases; Hematology; hepatomegaly; Humans; Infant, Newborn; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Membrane Proteins - deficiency; Other diseases. Semiology; Pedigree; seizures; stomatin; Syndrome; Nervous system diseases; Cataract; Congenital; Hematology; Epilepsy; Hepatic disease; Hemopathy; Hereditary; Cerebral disorder; Stomatocytosis; Variant; Cryohydrocytosis; Eye disease; Lens disease; Hemolytic anemia; Hepatomegaly; Dysfunction; congenital haemolytic anaemia; Central nervous system disease; Digestive diseases; seizures; Stomatin; cataracts; Anterior segment disease
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.04965.x

Summary This report concerns congenitally Na+–K+ leaky red cells of the ‘hereditary stomatocytosis’ class. Three new isolated cases and one new pedigree are described, and one previously reported case is expanded. In all cases, Western blotting of red cell membranes revealed a deficiency in the 32 kDa membrane protein, stomatin. All showed pronounced cation leaks at 37°C with markedly abnormal intracellular Na+ and K+ concentrations, like all other such stomatin‐deficient cases. Consistent with recent findings in two previously described British pedigrees, immunocytochemistry demonstrated that the deficiency of stomatin was not complete. On typical blood films, some red cells showed positive stomatin immunoreactivity, while most were negative, although in one case only a minority were negative. All platelets and neutrophils were stomatin positive. The cases differed markedly between themselves with regard to the temperature dependence of the passive leak to K+. Three showed a simple monotonic temperature dependence, while two showed a minimum at around 20–25°C, such that the cells were extremely leaky at 0°C, giving the phenotype known as ‘cryohydrocytosis’. These patients are the only two known cases of stomatin‐deficient cryohydrocytosis. Both showed a congenital syndrome of mental retardation, seizures, cataracts and massive hepatosplenomegaly, probably defining a new haemato‐neurological syndrome.