MedGen

Elliptocytosis is a hematologic disorder characterized by elliptically shaped erythrocytes and a variable degree of hemolytic anemia. Usually inherited as an autosomal dominant trait, elliptocytosis results from mutation in any one of several genes encoding proteins of the red cell membrane skeleton (summary by McGuire et al., 1988). Genetic Heterogeneity of Elliptocytosis Elliptocytosis-2 (130600) is caused by mutation in the SPTA1 gene (182860). Elliptocytosis-3 (617948) is caused by mutation in the SPTB gene (182870). Elliptocytosis-4 (166900), also known as Southeast Asian ovalocytosis, is caused by mutation in the SLC4A1 gene (109270). Also see pyropoikilocytosis (266140). See Delaunay (2007) for a discussion of the molecular basis of hereditary red cell membrane disorders. [from OMIM]

XLANP is an X-linked recessive hematologic disorder characterized by early-onset anemia and bone marrow erythroid hypoplasia with variable neutropenia. Some patients may have low platelets or platelet abnormalities. The severity is variable. Some patients have shown a favorable response to corticosteroid treatment (summary by Hollanda et al., 2006 and Sankaran et al., 2012). In some cases, the disorder may resemble Diamond-Blackfan anemia (see, e.g., DBA1; 105650) (Sankaran et al., 2012; Parrella et al., 2014; Klar et al., 2014). [from OMIM]

Any hereditary elliptocytosis in which the cause of the disease is a mutation in the SPTA1 gene. [from MONDO]

Southeast Asian ovalocytosis is a hereditary red blood cell disorder that is widespread in certain ethnic groups of Malaysia, Papua New Guinea, the Philippines, and Indonesia. Ovalocytic erythrocytes are rigid and exhibit reduced expression of many erythrocyte antigens. The ovalocytes are resistant to invasion in vitro by several strains of malaria, including Plasmodium falciparum and Plasmodium knowlesi (summary by Jarolim et al., 1991). The disorder is most often asymptomatic but has been reported to be associated with signs of mild hemolysis such as intermittent jaundice and gallstones (summary by Reardon et al., 1993). [from OMIM]

Hereditary elliptocytosis-3 (EL3) is a hemolytic disorder characterized by the presence of elliptical erythrocytes and resulting in some cases in hemolytic anemia (summary by Qualtieri et al., 1997). For a general description and a discussion of genetic heterogeneity of hereditary elliptocytosis (HE), see EL1 (611804). [from OMIM]

Hereditary pyropoikilocytosis was originally described by Zarkowsky et al. (1975) as a distinct hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells. HPP is a subset of hereditary elliptocytosis (see 611804) due to homozygous or compound heterozygous mutations in spectrin leading to severe disruption of spectrin self-association (review by An and Mohandas, 2008). [from OMIM]

TRNT1 deficiency encompasses what was first thought to be two separate disorders, a severe disorder called sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) and a milder disorder called retinitis pigmentosa with erythrocytic microcytosis (RPEM), each named for its most common features. SIFD begins in infancy, and affected individuals usually do not survive past childhood. RPEM, on the other hand, is recognized in early adulthood, and the microcytosis usually does not cause any health problems. However, it has since been recognized that some individuals have a combination of features that fall between these two ends of the severity spectrum. All of these cases are now considered part of TRNT1 deficiency.

In addition, many individuals with TRNT1 deficiency have recurrent fevers that are not caused by an infection. These fever episodes are often one of the earliest recognized symptoms of TRNT1 deficiency, usually beginning in infancy. The fever episodes are typically accompanied by poor feeding, vomiting, and diarrhea, and can lead to hospitalization. In many affected individuals, the episodes occur regularly, arising approximately every 2 to 4 weeks and lasting 5 to 7 days, although the frequency can decrease with age.

Many people with TRNT1 deficiency have an immune system disorder (immunodeficiency) that can lead to recurrent bacterial infections. Repeated infections can cause life-threatening damage to internal organs. The immunodeficiency is characterized by low numbers of immune system cells called B cells, which normally help fight infections by producing immune proteins called antibodies (or immunoglobulins). These proteins target foreign invaders such as bacteria and viruses and mark them for destruction. In many individuals with TRNT1 deficiency, the amount of immunoglobulins is also low (hypogammaglobulinemia).

A common feature of TRNT1 deficiency is a blood condition called sideroblastic anemia, which is characterized by a shortage of red blood cells (anemia). In TRNT1 deficiency, the red blood cells that are present are unusually small (erythrocytic microcytosis). In addition, developing red blood cells in the bone marrow (erythroblasts) can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment in the lab with certain dyes. These abnormal cells are called ring sideroblasts.

Neurological problems are also frequent in TRNT1 deficiency. Many affected individuals have delayed development of speech and motor skills, such as sitting, standing, and walking, and some have low muscle tone (hypotonia).

Eye abnormalities, often involving the light-sensing tissue at the back of the eye (the retina), can occur in people with TRNT1 deficiency. Some of these individuals have a condition called retinitis pigmentosa, in which the light-sensing cells of the retina gradually deteriorate. Eye problems in TRNT1 deficiency can lead to vision loss.

Features that occur less commonly in people with TRNT1 deficiency include hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss), recurrent seizures (epilepsy), and problems with the kidneys or heart.

TRNT1 deficiency is a condition that affects many body systems. Its signs and symptoms can involve blood cells, the immune system, the eyes, and the nervous system. The severity of the signs and symptoms vary widely. [from MedlinePlus Genetics]

Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis is an X-linked recessive disorder with onset of features in early childhood. Anemia is sometimes present. Some patients may show mild early motor or speech delay, but cognition is normal (summary by Andreoletti et al., 2017). [from OMIM]

The AMME complex is an X-linked contiguous gene deletion syndrome with features of Alport syndrome (see 301050), impaired intellectual development, midface hypoplasia, and elliptocytosis in affected males (summary by Meloni et al., 2002). [from OMIM]

Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) is characterized by severe progressive cerebropulmonary symptoms, resulting in death in infancy from respiratory failure. Features include malabsorption, progressive growth failure, recurrent infections, chronic hemolytic anemia, and transient liver dysfunction. Neuropathology shows increased angiomatosis-like leptomeningeal, cortical, and superficial white matter vascularization and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and granuloma-like lesions are seen in the lungs, and there is hepatomegaly with steatosis and collagen accumulation (Uusimaa et al., 2018). [from OMIM]

The presence of elliptical, cigar-shaped erythrocytes on peripheral blood smear. [from HPO]