Hereditary Disorders of Red Cell Permeability Clinical Presentation

Updated: Jan 30, 2019
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
  • Print
Presentation

History

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.

It is now recognized that stomatocytosis may occur in association with syndromes, including the following:

  • CHC with mental retardation, seizures, and hepatosplenomegaly
  • Nonleaky stomatocytosis with hypercholesterolemia, xanthomas, splenomegaly, and macrothrombocytopenia
  • DHSt with transient perinatal edema

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. [16]

A few case reports have documented DHSt in association with recurrent fetal loss or with hydrops fetalis (which, as previously mentioned, is a feature of the syndromic form of DHSt). The presence of perinatal effusions may require ascitic taps but is not a predictor of the severity of anemia later in life, and usually resolves in infancy. [17] The mechanism for this is uncertain but may involve hepatic dysfunction. [18]

Iron overload is common, and adults may be diagnosed with hemochromatosis. The mechanism for this is unknown. [19]

Intermediate syndromes

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.

Next:

Physical

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. The presence of xanthomas, splenomegaly, bleeding tendency, seizure disorder, or mental retardation would suggest syndromic stomatocytosis. Evaluate signs of cardiovascular compromise in patients who are ill. Monitor growth parameters yearly in children. Monitor ferritin levels for iron overload.

Previous