Histiocytosis-plus lymphadenopathy syndrome ... (Histiocytosis-lymphadenopathy syndrome plus) - Gen SLC29A3.

Histiocytosis syndrome lymphadenopathy-plus, also known as SLC29A3 spectrum disorders, is a group of diseases with signs and symptoms overlap and affecting many parts of the body. This group of disorders includes H syndrome, hypertrichosis pigmented with diabetes mellitus syndrome (IDHP), histiocytosis Faisalabad and Rosai-Dorfman disease family, also known as sinus histiocytosis with massive lymphadenopathy or HSLM.

A common characteristic of changes in this spectrum is histiocytosis, characterized by the presence of abnormal cells in one or more body tissues, which can lead to damaged tissues or organs. Often this accumulation occurs in the lymph nodes, leading to lymphadenopathy. Other areas of accumulation of cells may include skin, kidney, central nervous system or digestive tract. This spectrum is known as lymphadenopathy syndrome histiocytosis-plus because alterations that make up the spectrum may have additional signs and symptoms.

A characteristic feature of the syndrome H, are lesions of the skin, typically in the bottom of the body. These lesions are characterized by hyperpigmentation and hypertrichosis. In addition, histiocytes accumulate at the site of skin lesions. Other features include hepatomegaly H syndrome, cardiac abnormalities, hearing loss, hypogonadism and short stature. As syndrome H, IDHP hyperpigmented skin areas generated with hypertrichosis. IDHP also characterized by the development of type 1 diabetes, which usually begins in childhood. Type 1 diabetes occurs when the body does not produce enough of the hormone insulin, which leads to dysregulation of glucose concentrations in blood. Meanwhile, Faisalabad histiocytosis usually generates lymphadenopathy and eyelid swelling due to accumulation of histiocytes. Affected individuals may also have joint deformities on the toes or feet and hearing loss. On the other hand, the most common characteristic of Rosai-Dorfman disease is lymphadenopathy family, which usually affects the lymph nodes in the neck. Histiocytes may also accumulate in other parts of the body.

This process is due to mutations in the SLC29A3 gene, located on the long arm of chromosome 10 (10q22.1). This gene encodes a transporter protein called balancer nucleoside 3 (ENT3). ENT3 is in the membranes surrounding the lysosomes and mitochondria. It is believed that this protein carries nucleosides generated by the decomposition of DNA and RNA in the cell lysosomes so they can be reused. Meanwhile, it is believed that the ENT3 protein in mitochondrial membranes aid nucleoside transport into mitochondria, so that can be used for forming or repairing DNA and mitochondrial RNA, which are essential for the proper functioning of the structures .

SLC29A3 gene mutations involved in this spectrum changes reduce or eliminate the activity of the protein ENT3. Although it is unclear how the loss of ENT3 activity generates histiocytosis and other features of histiocytosis-lymphadenopathy plus syndrome it is likely that the consequent deterioration nucleoside transport leads to an accumulation of nucleosides in lysosomes and possibly other cellular structures. Nucleosides excess can be detrimental to cell function. The absence or deficiency of activity ENT3 can also lead to a reduction in the number of nucleosides in the mitochondria, which could affect cellular energy production, which would affect many systems organsimo. It is unclear how the SLC29A3 gene mutations lead to different patterns of signs and symptoms, even within the same family.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with histiocytosis-plus lymphadenopathy syndrome by complete PCR amplification of exons SLC29A3 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).