Pompe disease

Pompe disease is an inherited, neuromuscular condition that causes muscle weakness in people of all ages. Symptoms may first occur at any time from infancy to adulthood. Pompe is also known as acid maltase deficiency or glycogen storage disease type 2.

Trisomy 18 (full article)

Source: Anna Cereda M.D and John C Carey M.D Orphanet Journal of Rare Diseases

Definition

The trisomy 18 syndrome, also known as Edwards syndrome, is a common autosomal chromosomal disorder due to the presence of an extra chromosome 18. The first reported infants were described in 1960 by Edwards et al. and Smith et al. [1,2]. The syndrome pattern comprises a recognizable pattern of major and minor anomalies, an increased risk of neonatal and infant mortality, and significant psychomotor and cognitive disability.

Trisomy 18 (in short)

Source: Anna Cereda M.D and John C Carey M.D Orphanet Journal of Rare Diseases

• The trisomy 18 syndrome, also known as Edwards syndrome, is a common chromosomal disorder due to the presence of an extra chromosome 18, either full, mosaic trisomy, or partial trisomy 18q.
• The condition is the second most common autosomal trisomy syndrome after trisomy 21. 
• The live born frequency is estimated as 1/6,000-1/8,000, but the overall frequency is higher (1/2500-1/2600) due to the high frequency of fetal loss and pregnancy termination after prenatal diagnosis. 
• The frequency of trisomy 18 rises with the increasing maternal age. 
• The recurrence risk for a family with a child with full trisomy 18 is about 1%.
• Currently most cases of trisomy 18 are prenatally diagnosed, based on screening by maternal age, maternal serum marker screening, or detection of sonographic abnormalities (e.g., increased nuchal translucency thickness, growth retardation, choroid plexus cyst, overlapping of fingers, and congenital heart defects ). 
• The recognizable syndrome pattern consists of major and minor anomalies, prenatal and postnatal growth deficiency, an increased risk of neonatal and infant mortality, and marked psychomotor and cognitive disability. Typical minor anomalies include characteristic craniofacial features, clenched fist with overriding fingers, small fingernails, underdeveloped thumbs, and short sternum. The presence of major malformations is common, and the most frequent are heart and kidney anomalies. Feeding problems occur consistently and may require enteral nutrition.
• Despite the well known infant mortality, approximately 50% of babies with trisomy 18 live longer than 1 week and about 5-10% of children beyond the first year. 
• The major causes of death include central apnea (suspension of  breathing), cardiac failure due to cardiac malformations, respiratory insufficiency due to hypoventilation, aspiration, or upper airway obstruction and, likely, the combination of these and other factors (including decisions regarding aggressive care). Upper airway obstruction is likely more common than previously realized and should be investigated when full care is opted by the family and medical team. 
• The complexity and the severity of the clinical presentation at birth and the high neonatal and infant mortality make the perinatal and neonatal management of babies with trisomy 18 particularly challenging, controversial, and unique among multiple congenital anomaly syndromes. Health supervision should be diligent, especially in the first 12 months of life, and can require multiple pediatric and specialist evaluations. 

Gaucher disease

Source: Nadia BELMATOUG MD; Jérôme STIRNEMANN MD. Orphanet 


Gaucher disease is a rare inherited disorder, in which people do not have enough of an enzyme called acid beta-glucosidase, which normally breaks down a fatty waste product called glucosylceramide. Without the enzyme, glucosylceramide builds up in the body, typically in the liver, spleen and bone marrow, which produces the symptoms of the disease: anaemia (low red blood cell counts), tiredness, easy bruising and a tendency to bleed, an enlarged spleen and liver, and bone pain and breaks.

Gaucher disease (GD) is a lysosomal storage disorder encompassing three main forms (types 1, 2 and 3), a fetal form and a variant with cardiac involvement (Gaucher disease - ophthalmoplegia - cardiovascular calcification or Gaucher-like disease).


Frequency

The frequency is approximately 1/100,000. The annual incidence of GD in the general population is about 1/60,000, but it can reach up to 1/1,000 in Ashkenazi Jewish populations.

Symptoms

The clinical manifestations of this disease are highly variable.

• Type 1 (90% of cases) is the chronic and non-neurological form associated with organomegaly (spleen, liver), bone anomalies (pain, osteonecrosis, pathological fractures) and cytopenia. 
• Type 2, the acute neurological form, is characterized by early onset, rapidly progressing brainstem dysfunction, associated with organomegaly and leading to death before the age of 2. 
• Type 3, the subacute neurological form, affects children or adolescents and is characterized by progressive encephalopathy (oculomotor apraxia, epilepsy and ataxia) with the systemic manifestations seen in type 1. The fetal form manifests with a decrease or absence of fetal movements or anasarca. Gaucher-like disease presents with progressive calcification of the aorta and the aortic and/ or mitral valves as its main feature.

Genetics

GD is due to mutations in the GBA gene (1q21) that codes for a lysosomal enzyme, glucocerebrosidase, or in very rare cases the PSAP gene that codes for its activator protein (saposin C). The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, the spleen and the bone marrow (Gaucher cells).
Transmission is autosomal recessive.

Diagnosis

Formal diagnosis of the disease is determined by the measurement of glucocerebrosidase levels in circulating leukocytes. Genotyping confirms the diagnosis.

Differential diagnoses include other lysosomal storage disorders. The presence of Gaucher-like cells can be found in certain hematologic diseases (lymphoma, Hodgkin's lymphoma and chronic lymphocytic leukemia; see these terms).

Treatments

There are two available treatments for GD type 1 and 3: enzyme substitution therapy (using imiglucerase or velaglucerase) and substrate reduction therapy (miglustat). These treatments are ineffective for GD type 2.

Prognosis

The prognosis is good in GD type 1.
In type 2, death usually occurs before the age of 2. Without specific treatment,
GD type 3 progresses to death within a few years.

Hemophilia

Tsarevich of Russia

Authors:  Antonio Liras MD, Cristina Segovia MD and Aline S Gabán MD. Orphanet journal of rare diseases   

Hemophilia is a recessive X-linked hereditary disorder (X-linked recessive diseases usually occurs in males who have inherited a recessive X-linked mutation from their mother) caused by a deficiency of coagulation factor VIII (hemophilia A) or IX (hemophilia B). The disease is considered to be severe when factor levels are below 1% of normal values, moderate when they are between 1 and 5% and mild when levels range between 5% and 40% [1].

Huntington disease

Source: Pr  Raymund ROOS MD. Orphanet. January 2011

What's Huntington Disease?

Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia.