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Retinitis pigmentosa and erythrocytic microcytosis(RPEM)

MedGen UID:
934743
Concept ID:
C4310776
Disease or Syndrome
Synonym: RPEM
 
Gene (location): TRNT1 (3p26.2)
 
Monarch Initiative: MONDO:0014850
OMIM®: 616959

Definition

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.

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.

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.

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.

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]

Clinical features

From HPO
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Anisocytosis
MedGen UID:
66371
Concept ID:
C0221278
Finding
Abnormally increased variability in the size of erythrocytes.
Poikilocytosis
MedGen UID:
67451
Concept ID:
C0221281
Finding
The presence of abnormally shaped erythrocytes.
Hypochromia
MedGen UID:
87187
Concept ID:
C0333912
Finding
A qualitative impression that red blood cells have less color than normal when examined under a microscope, usually related to a reduced amount of hemoglobin in the red blood cells.
Elliptocytosis
MedGen UID:
98107
Concept ID:
C0427480
Finding
The presence of elliptical, cigar-shaped erythrocytes on peripheral blood smear.
Decreased mean corpuscular volume
MedGen UID:
1375398
Concept ID:
C0855790
Finding
A reduction from normal of the mean corpuscular volume, or mean cell volume (MCV) of red blood cells (usually defined as an MCV below 80 femtoliters).
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Decreased circulating iron concentration
MedGen UID:
65918
Concept ID:
C0235988
Finding
The concentration of iron in the blood circulation is below the lower limit of normal.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Night blindness
MedGen UID:
10349
Concept ID:
C0028077
Disease or Syndrome
Inability to see well at night or in poor light.
Macular edema
MedGen UID:
75732
Concept ID:
C0271051
Disease or Syndrome
Thickening of the retina that takes place due to accumulation of fluid in the macula as a nonspecific response to blood-retinal barrier breakdown. Macular edema is a common pathological response to a wide variety of ocular insults, most commonly after intraocular (e.g. cataract) surgery or in association with retinal vascular (e.g. diabetic eye disease, retinal vein occlusion) or inflammatory (e.g. uveitis) disease.
Preretinal fibrosis
MedGen UID:
87388
Concept ID:
C0339543
Anatomical Abnormality
An epiretinal membrane is a thin sheet of fibrous tissue that can develop on the surface of the macular area of the retina and cause a disturbance in vision. An epiretinal membrane area can develop on the thin macular area of the retin. An epiretinal membrane is also sometimes called a macular pucker, premacular fibrosis, surface wrinkling retinopathy or cellophane maculopathy.
Ring scotoma
MedGen UID:
140951
Concept ID:
C0438434
Finding
An annular field defect centered on fixation.
Retinal atrophy
MedGen UID:
101075
Concept ID:
C0521694
Disease or Syndrome
Well-demarcated area(s) of partial or complete depigmentation in the fundus, reflecting atrophy of the retinal pigment epithelium with associated retinal photoreceptor loss.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Bone spicule pigmentation of the retina
MedGen UID:
323029
Concept ID:
C1836926
Finding
Pigment migration into the retina in a bone-spicule configuration (resembling the nucleated cells within the lacuna of bone).
Retinal pigment epithelial atrophy
MedGen UID:
333564
Concept ID:
C1840457
Finding
Atrophy (loss or wasting) of the retinal pigment epithelium observed on fundoscopy or fundus imaging.
Attenuation of retinal blood vessels
MedGen UID:
480605
Concept ID:
C3278975
Finding
Peripheral retinal atrophy
MedGen UID:
765930
Concept ID:
C3553016
Finding
Photoreceptor layer loss on macular OCT
MedGen UID:
892581
Concept ID:
C4073079
Finding
Loss of the outer nuclear layer (photoreceptor layer) as assessed by ocular coherence tomography.

Recent clinical studies

Etiology

DeLuca AP, Whitmore SS, Barnes J, Sharma TP, Westfall TA, Scott CA, Weed MC, Wiley JS, Wiley LA, Johnston RM, Schnieders MJ, Lentz SR, Tucker BA, Mullins RF, Scheetz TE, Stone EM, Slusarski DC
Hum Mol Genet 2016 Jan 1;25(1):44-56. Epub 2015 Oct 22 doi: 10.1093/hmg/ddv446. PMID: 26494905Free PMC Article

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