Hereditary Disorders of Red Cell Permeability Clinical Presentation
- Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Max J Coppes, MD, PhD, MBA more...
The hereditary stomatocytosis syndromes and allied disorders are usually transmitted in an autosomal dominant pattern, although sporadic cases have been reported. Penetrance varies, with significant disparity in clinical symptoms between affected individuals in the same kindred.
Many patients present with hemolytic anemia in the neonatal period, but others are asymptomatic throughout their lifetime. Aplastic crises associated with parvovirus and other infections have been reported. An unusual characteristic of the stomatocytosis syndromes is a predisposition to severe life-threatening thrombosis after splenectomy.
A number of acquired conditions are associated with stomatocytes in the blood, although these patients do not usually have hematologic symptoms. Stomatocytosis may also be observed with inherited conditions such as Mediterranean stomatocytosis, which does not affect erythrocyte permeability and has an accompanying thrombocytopenia.
Overhydrated hereditary stomatocytosis (OHSt)
The degree of hemolysis and anemia varies. Moderate-to-severe lifelong hemolytic anemia is most typical. A few reports described patients who experienced symptoms of vaso-occlusion, such as dyspnea, chest pain, and abdominal pain, particularly after splenectomy.
Anemia is generally not present at birth, but neonatal jaundice is relatively common and is occasionally serious enough to warrant exchange transfusion. Patients with severe disease are usually younger than 6 months at presentation.
Dehydrated hereditary stomatocytosis (DHSt)
This is the most common form of the hereditary stomatocytosis syndromes. Patients typically present with mild-to-moderate hemolytic anemia. Periodic episodes of jaundice are common. Most patients are asymptomatic, although easy fatigability is a common symptom.
A few case reports have documented DHSt in association with recurrent fetal loss or with hydrops fetalis. The presence of perinatal effusions may require ascitic taps but is not a predictor of the severity of anemia later in life. The mechanism for this is uncertain but may involve hepatic dysfunction.
Patients with intermediate syndromes do not have consistent hemolytic anemia.
Cryohydrocytosis (CHC) is an intermediate syndrome in which erythrocytes undergo spontaneous in vitro hemolysis after storage at 4°C.
Familial pseudohyperkalemia (FP) manifests with factitious hyperkalemia. Red cell macrocytosis is rare.
Focus the physical examination on organ systems affected by hemolytic anemia. Pallor, jaundice, hepatosplenomegaly, and signs of gallstone disease are the most likely physical findings. Evaluate signs of cardiovascular compromise in patients who are ill. Monitor growth parameters yearly in children. Monitor ferritin levels for iron overload.
As described above, the hereditary stomatocytosis disorders and allied syndromes are all inherited in an autosomal dominant fashion. Dehydrated hereditary stomatocytosis and some cases of FP map to chromosome band 16q23-24. CHC is associated with mutations of band 3 (AE1). Overhydrated hereditary stomatocytosis has been associated with mutations of RHAG.
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