Congenital Hypoplastic Anemia

Introduction:

Congenital hypoplastic anemia is a rare condition observed at two to three months of age. In one-third of the patients, children born with this condition develop short stature or other congenital abnormalities. Most of the cases develop due to mutation of genes seen in the ribosomal proteins.

What Causes Congenital Hypoplastic Anemia?

Diamond-Blackfan anemia is the other name for congenital hypoplastic anemia. Diamond-Blackfan anemia is a black condition characterized by a low red blood cell count. This anemia is caused due to bone marrow failure to produce sufficient RBCs. Diamond-Blackfan anemia can lead to aplastic syndromes, where there is a complete absence of RBCs.

Congenital disorders are conditions present at birth or develop within one-year post-birth. Congenital hypoplastic anemia is caused due to insufficient or absence of red blood precursor cells in the bone marrow. It is associated with familial history or is autosomally dominant in about 40 to 45 percent of cases. The primary cause for such congenital anemia is the unnatural death of red blood cells or apoptosis. Such apoptosis is caused due to mutations seen in specific ribosomal proteins, such as.

• RPS19 gene on Chromosome 19.

• RPS24 gene on Chromosome 10.

• RPS17 gene on Chromosome 15.

High levels of erythropoietin are present in the serum of Diamond-Blackfan syndrome.

Who Is at More Risk of Developing Congenital Hypoplastic Anemia?

As the name suggests, congenital hypoplastic anemia is seen in children. About 92 percent of the total cases are during infancy, and about 25 percent are present during birth. It is more commonly seen between two to six months of age. The chances of fluid buildup (hydrops fetalis) in the organs and tissues are very rare with this condition.

What Are the Risk Factors Associated With Hypoplastic Anemia in Children?

Some commonly encountered congenital anomalies associated with hypoplastic anemia include the following.

• 50 percent of cases have congenital anomalies.

• 21 percent of cases have more than one anomaly in an individual.

• 25 percent of cases show multiple anomalies.

What Are the Common Signs Seen in Congenital Hypoplastic Anemia?

Some of the signs observed around the eyes are:

• Strabismus: This is an eye disorder where the eyes do not align appropriately while looking at an object. It can affect either a single eye or both eyes. In some cases, it occurs rarely, and in others, it occurs throughout the lifetime.

• Congenital Cataract: It affects either one or both eyes. It is caused due to the opacity of the eye lens. The condition may worsen with age and may cause partial blindness.

• Congenital Glaucoma: It is caused due to increased pressure in the eye chambers. It usually occurs after childbirth. This can lead to permanent blindness in children.

Signs observed in the neck region are:

• Short: Children with congenital hypoplastic anemia have shorter necks.

• Webbing: It is seen as the fusion of two or more fingers together as a single unit.

• Sprengel Deformity: This is a skeletal defect in the scapula bone on the back of the neck. One shoulder blade is higher than the other due to the failure in fetal development.

• Klippel Feil Syndrome: This is a congenital disability due to the abnormal fusion of more than one cervical vertebra. The child shows restricted neck movement, shortness of breath, and a low hairline.

Signs seen in the musculoskeletal region account for about 30 percent of cases, especially in the upper limb. Some of the clinical features seen are:

• Absence of Radial Pulse: Radial pulse is noted at the hand wrist region. The absence of a radial pulse indicates the abnormal origin of the radial artery.

• Flat Thenar Eminence: The thenar eminence is a fleshy area seen below the thumb region. These muscles are responsible for the flexible movement of thumbs. During congenital anomalies, these surfaces are seen as flattened structures.

• Triphalangeal Bifidor Duplex or Hypoplastic Thumb: Triphalangeal thumb is the presence of an additional thumb, the bifid thumb is seen as the duplication of thumb having two thumb heads from a single thumb, the duplex finger is the bending of fingers towards the palm, and hypoplastic thumb is a condition where the thumb is small or completely absent.

• Syndactyly: It is seen as the fusion of two digits or toes.

Abnormalities associated with other organs are:

• Urogenital Defect: About 38 percent of the cases show urogenital defects such as hypospadias, where the urethra fails to open from the straight end of the penis and opens from below near the scrotum.

• Kidneys: The kidneys are absent or are horseshoe-shaped kidneys.

• Heart: Congenital hypoplastic anemia can result in a hole in the atrium of the heart causing atrial septal defect (ASD), or a hole in the ventricle of the heart, causing ventricular septal defect (VSD). It can also cause narrowing of the aorta or coarctation of the aorta and complex congenital heart disease in children.

Other signs include:

• Short stature.

• Learning difficulties.

• Hypothyroidism.

• Renal failure.

What Are the Other Conditions That May Look Similar to Congenital Hypoplastic Anemia?

Other differential diagnoses with similar signs and symptoms are as follows:

• Transient erythroblastopenia of childhood.

• Hemolytic disease of the newborn.

• Aplastic crises caused by Parvovirus B19 in various chronic hemolytic anemias.

• Intrauterine Parvovirus B19 infection.

• Fanconi anemia.

• Shwachman - Diamond syndrome.

• Pearson syndrome.

How to Manage Congenital Hypoplastic Anemia?

• Medical Management: Children above one year of age are given corticosteroid therapy. Drugs like Prednisone 2 mg/ kg/ 24 hours are given. Once the hemoglobin (Hb) level starts increasing, the dosage can be reduced. The rate of response is as great as 80 percent. The Hb normalizes within four to six weeks, and the RBC (red blood cells) increases within one to three weeks.

• Blood Transfusion: Blood can be transfused from a donor to maintain an acceptable Hb level.

• Bone Marrow Transplantation: Children with twins can undergo an allogenic transplant donor (HLA) of bone marrow.

What Are the Laboratory Findings of Congenital Hypoplastic Anemia?

The following inferences can be made based on the following examinations.

• Blood Hemoglobin: It is low, suggesting anemia. Increased HbF or fetal hemoglobin was observed.

• Mean Corpuscular Value (MCV): High MCV shows macrocytic red blood cells.

• Other Blood Findings: Shows low reticulocyte, no hypersegmented neutrophils, low platelet count or thrombocytopenia, increased erythrocyte adenosine deaminase (ADA), and serum iron level is elevated.

• Chemical Antigen Test: Shows high ‘i’ antigen occasionally.

• Bone Marrow Biopsy: The RBC precursors are decreased. Other cellular elements are normal.

• Chromosomal Studies: No abnormalities are detected, like the breaking of chromosomes.

Conclusion:

Congenital hypoplastic anemia is a premalignant condition. It can develop into malignancies like acute myeloid leukemia (AML) in about five percent of cases and rarely may develop into solid tumors like osteosarcoma. Most remission occurs within the first decade of life. Patients undergoing blood transfusions are at higher risk of complications like an overload of iron in the body or hemosiderosis in organs and tissues. Early detection of disease helps in early treatment and a faster recovery rate.