{"id":2056,"date":"2023-06-19T19:37:05","date_gmt":"2023-06-19T16:37:05","guid":{"rendered":"https:\/\/integris.gr\/spanies-kai-genetikes-metavolikes-pathiseis\/"},"modified":"2026-01-14T11:19:08","modified_gmt":"2026-01-14T09:19:08","slug":"spanies-kai-genetikes-metavolikes-pathiseis","status":"publish","type":"page","link":"https:\/\/integris.gr\/en\/spanies-kai-genetikes-metavolikes-pathiseis\/","title":{"rendered":"Rare and Genetic Metabolic Diseases"},"content":{"rendered":"

[vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” rt_padding_bottom=”0″][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll”][vc_empty_space height=”180px” el_class=”keno”][vc_column_text]<\/p>\n\n\n\n
\n
Rare and Genetic Metabolic Diseases<\/strong><\/div>\n<\/td>\n
\n
Rare diseases are those that affect a small number of individuals compared to the general population.<\/div>\n

 <\/p>\n

According to the definition by the European Union (EU), a disease is considered rare when it affects 5 out of 10,000 people in the community.1<\/sup>
\nIt is estimated that in Greece, approximately 350,000 to 600,000 people are affected by rare diseases, and over 30 million people in Europe.2<\/sup>
\nIn total, there have been around 6,000 to 8,000 rare diseases recorded globally. Of these, 72% are genetic, while others result from infections, cancers, allergies, and environmental factors. To this day, the cause of many rare diseases remains unknown3,4<\/sup><\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

[\/vc_column_text][vc_column_text]<\/p>\n\n\n\n\n
\n
Rare and Genetic Metabolic Diseases<\/strong><\/div>\n<\/td>\n<\/tr>\n
<\/td>\n\n
Rare diseases are those that affect a small number of individuals compared to the general population.<\/div>\n

 <\/p>\n

According to the definition by the European Union (EU), a disease is considered rare when it affects 5 out of 10,000 people in the community.1<\/sup>
\nIt is estimated that in Greece, approximately 350,000 to 600,000 people are affected by rare diseases, and over 30 million people in Europe.2<\/sup>
\nIn total, there have been around 6,000 to 8,000 rare diseases recorded globally. Of these, 72% are genetic, while others result from infections, cancers, allergies, and environmental factors. To this day, the cause of many rare diseases remains unknown.3,4<\/sup><\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

[\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”fullwidth” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” rt_padding_left=”0″ rt_padding_right=”0″ rt_padding_bottom=”95px”][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_padding_left=”0″ rt_padding_right=”0″][vc_raw_html el_class=”spanies”]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[\/vc_raw_html][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row”][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll”][vc_column_text el_class=”span_kei_tx”]<\/p>\n

Common symptoms can sometimes mask underlying rare diseases, leading to misdiagnosis and treatment delays.4<\/sup>
\nTherefore, while these conditions may differ, they all present similar clinical challenges, since many healthcare professionals may lack experience in recognizing or managing the majority of rare diseases. As a result, diagnosis is often delayed or inaccurate, making optimal clinical management more difficult.5<\/sup><\/p>\n

Sources<\/span><\/p>\n

    \n
  1. https:\/\/eody.gov.gr\/disease\/spania-nosimata\/<\/li>\n
  2. https:\/\/rarediseasesgreece.gr\/<\/li>\n
  3. https:\/\/www.eurordis.org\/<\/li>\n
  4. https:\/\/www.orpha.net\/<\/li>\n
  5. Haendel M, Vasilevsky N, Unni D, Bologa C, Harris N, Rehm H, Hamosh A, Baynam G, Groza T, McMurry J, Dawkins H, Rath A, Thaxon C, Bocci G, Joachimiak MP, K\u00f6hler S, Robinson PN, Mungall C, Oprea TI. How many rare diseases are there? Nat Rev Drug Discov. 2020 Feb;19(2):77-78. doi: 10.1038\/d41573-019-00180-y. PMID: 32020066; PMCID: PMC7771654.)<\/li>\n<\/ol>\n

    [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row”][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll”][vc_column_text]<\/p>\n\n\n\n\n
    Polyneuropathy in Hereditary<\/td>\n<\/tr>\n
    <\/td>\n\n
    Transthyretin Amyloidosis<\/strong>
    \n(hATTR)<\/div>\n

     <\/p>\n

    \n

    Hereditary transthyretin amyloidosis (hATTR) is a rare hereditary disorder caused by mutations in the gene responsible for the expression of the transthyretin protein (TTR).<\/p>\nRead More<\/a><\/span>\n


    \nThese mutations destabilize transthyretin, causing it to dissociate, misfold,and aggregate into amyloid fibrils. These amyloid fibrils deposit in various organs of the body, leading to the broad, multisystemic manifestations seen in hATTR.<\/p>\n

    The peripheral nervous system (both autonomic and somatic) and the heart are two organs that are commonly affected.1<\/sup><\/p>\n

    Polyneuropathy in hereditary transthyretin amyloidosis typically presents as progressive peripheral neuropathy with predominantly sensory involvement.2<\/sup><\/p>\n

    Since the initial symptoms may be vague and attributed to more common conditions, early and accurate diagnosis can be relatively challenging.<\/p>\n

    Delays in the diagnosis of ATTR can have serious consequences for patients who may eventually develop end-stage organ failure. The development of new therapies that appear to be more effective when initiated early, makes it imperative for clinicians to promptly recognize the signs and symptoms indicative of the disease.3<\/sup><\/p>\n

    Sources<\/span><\/p>\n

      \n
    1. Manganelli F, Fabrizi GM, Luigetti M, Mandich P, Mazzeo A, Pareyson D. Hereditary transthyretin amyloidosis overview. Neurol Sci. 2022 Dec;43(Suppl 2):595-604. doi: 10.1007\/s10072-020-04889-2. Epub 2020 Nov 14. PMID: 33188616; PMCID: PMC9780126)<\/li>\n
    2. V\u00e9lez-Santamar\u00eda V, Nedkova-Hristova V, Morales de la Prida M, Casasnovas C. Hereditary Transthyretin Amyloidosis with Polyneuropathy: Monitoring and Management. Int J Gen Med. 2022 Dec 20;15:8677-8684. doi: 10.2147\/IJGM.S338430. PMID: 36573111; PMCID: PMC9789700.<\/li>\n
    3. Benson MD, Dasgupta NR, Rao R. Diagnosis and Screening of Patients with Hereditary Transthyretin Amyloidosis (hATTR): Current Strategies and Guidelines. Ther Clin Risk Manag. 2020 Aug 14;16:749-758. doi: 10.2147\/TCRM.S185677. PMID: 32884276; PMCID: PMC7434568<\/li>\n<\/ol>\n

      <\/div>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

      [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row”][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_padding_left=”0″][vc_column_text]<\/p>\n\n\n\n\n
      Familial Chylomicronemia<\/span><\/td>\n<\/tr>\n
      \"\"<\/td>\n\n
      Syndrome<\/strong> (FCS)<\/div>\n

       <\/p>\n

      Familial Chylomicronemia Syndrome (FCS) is a rare hereditary disorder with an estimated prevalence of 1\/1,000,000 in the population, although it is possibly under-recognized and under-diagnosed.1<\/sup><\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nRead More<\/a><\/span>\n
      \n
      \n

      It is characterized by the loss of lipoprotein lipase activity, resulting in the accumulation of chylomicrons in the plasma and significantly elevated triglyceride levels, 10 to 100 times higher than normal.1,2<\/sup><\/p>\n

      The increased triglycerides lead to several complications in patients, with the most severe being recurrent episodes of acute pancreatitis, a potentially life-threatening complication.<\/p>\n

      Therefore, identifying patients with FCS for the administration of appropriate treatment that would mitigate the risk of acute pancreatitis is extremely important.<\/p>\n

      Sources<\/span><\/p>\n

        \n
      1. (Ueda M. Familial chylomicronemia syndrome: importance of diagnostic vigilance. Transl Pediatr. 2022 Oct;11(10):1588-1594. doi: 10.21037\/tp-22-488. PMID: 36345451; PMCID: PMC9636463)<\/li>\n
      2. Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O\u2019Dea L, Bruckert E. Volanesorsen and
        \nTriglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056\/ NEJMoa1715944. PMID: 31390500)<\/li>\n<\/ol>\n<\/div>\n

        <\/div>
        \n[\/vc_column_text][vc_column_text]<\/p>\n\n\n\n\n\n
        \"\"<\/td>\n<\/tr>\n
        Familial Chylomicronemia<\/td>\n<\/tr>\n
        <\/td>\n\n
        Syndrome<\/strong> (FCS)<\/div>\n

         <\/p>\n

        \n

        Familial Chylomicronemia Syndrome (FCS) is a rare hereditary disorder with an estimated prevalence of 1\/1,000,000 in the population, although it is possibly under-recognized and under-diagnosed.1<\/sup><\/p>\nRead More<\/a><\/span>\n


        \nIt is characterized by the loss of lipoprotein lipase activity, resulting in the accumulation of chylomicrons in the plasma and significantly elevated triglyceride levels, 10 to 100 times higher than normal.1,2<\/sup><\/p>\n

        The increased triglycerides lead to several complications in patients, with the most severe being recurrent episodes of acute pancreatitis, a potentially life-threatening complication.<\/p>\n

        Therefore, identifying patients with FCS for the administration of appropriate treatment that would mitigate the risk of acute pancreatitis is extremely important.<\/p>\n

        Sources<\/span><\/p>\n

          \n
        1. (Ueda M. Familial chylomicronemia syndrome: importance of diagnostic vigilance. Transl Pediatr. 2022 Oct;11(10):1588-1594. doi: 10.21037\/tp-22-488. PMID: 36345451; PMCID: PMC9636463)<\/li>\n
        2. Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O\u2019Dea L, Bruckert E. Volanesorsen and
          \nTriglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019 Aug 8;381(6):531-542. doi: 10.1056\/ NEJMoa1715944. PMID: 31390500)<\/li>\n<\/ol>\n

          <\/div>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

          [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row” rt_padding_top=”0″][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll”][vc_column_text]<\/p>\n\n\n\n\n
          Mucopolysaccharidosis Type VII<\/td>\n<\/tr>\n
          <\/td>\n\n
          (MPS VII or Sly Syndrome)<\/div>\n

           <\/p>\n

          \n

          Mucopolysaccharidosis Type VII (MPS VII) is an ultra rare, heterogeneous, progressive neuro-metabolic disorder caused by a deficiency of the lysosomal enzyme \u03b2-glucuronidase1,2<\/sup>.<\/p>\nRead More<\/a><\/span>\n


          \nThe deficiency of \u03b2-glucuronidase results in the accumulation of glycosaminoglycans (GAGs) within the lysosomes of various body tissues, causing multi-organ damage, decreased cognitive function, and reduced life expectancy3<\/sup>. GAGs are essential components of the extracellular matrix and hold the key in functions such as angiogenesis, cell adhesion, cellular growth, and organogenesis4<\/sup>.<\/p>\n

          It is estimated that there are 200 MPS VII patients worldwide, but the disease’s frequency\/incidence may be underestimated since many patients present with idiopathic hydrops fetalis and may not survive before a diagnosis is established. Additionally, individuals with mild disease forms may remain asymptomatic throughout their lives1,3<\/sup>.<\/p>\n

          MPS VII is inherited in an autosomal recessive manner. The most common characteristics of the disease, apart from hydrops fetalis, include specific morphological features, growth disturbances, a characteristic short stature, recurrent ear and lower respiratory infections, cardiac problems, hernias, hepatomegaly, splenomegaly, and intellectual impairment of varying severity1<\/sup>. Symptoms may be present from the prenatal period or after birth5<\/sup>.<\/p>\n

          The diagnosis of the disease postnatally is based on measuring GAGs in urine, assessing enzyme activity, and performing the necessary genetic testing3<\/sup>.<\/p>\n

          The rarity and heterogeneity of the disease, physician’s limited awareness, and restricted access to diagnostic tools are factors contributing to delayed diagnosis1,5<\/sup>.<\/p>\n

            \n
          1. J Med Genet. 2016;53:403;<\/li>\n
          2. Genet Med 2017;19:983 988<\/li>\n
          3. Rheumatology ( Oxford). 2011; suppl 5):v4;<\/li>\n
          4. Crit Care . 2006;10:237; 2.<\/li>\n
          5. Genet Med 2017;19:983 988;<\/li>\n<\/ol>\n

            <\/div>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

            [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row” rt_padding_top=”0″][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll”][vc_column_text]<\/p>\n\n\n\n\n
            Long-Chain<\/td>\n<\/tr>\n
            <\/td>\n\n
            Fatty Acid Oxidation Disorders<\/strong> (LC-FAODs)<\/div>\n

             <\/p>\n

            \n

            Fatty acid oxidation disorders (FAODs) are a group of rare diseases with an autosomal recessive inheritance pattern and are associated with significant morbidity and mortality1<\/sup>.<\/p>\nRead More<\/a><\/span>\n


            \nFatty acids (short-chain, medium-chain, long-chain, or very long-chain) are utilized by the body as an energy source. To produce energy, they enter the mitochondria (organelles of eukaryotic cells) and undergo \u03b2-oxidation, a metabolic process involving a series of enzymes.<\/p>\n

            Long-chain fatty acid oxidation disorders (LC-FAODs) result from the malfunction of enzymes involved in the transport and\/or beta-oxidation of long-chain fatty acids, leading to the accumulation of toxic substances in the tissues of organs.<\/p>\n

            Clinical symptoms of the disease vary in severity and can range from muscle fatigue during physical activity in adults to cardiomyopathy and sudden death in neonates and infants. Common symptoms include hypoglycemia, liver dysfunction, skeletal and cardiac myopathy, rhabdomyolysis, and retinopathy2<\/sup>.<\/p>\n

            The diagnosis of LC-FAODs can be made at birth through a preventive metabolic disease screening. Currently, LC-FAODs are not included in the conditions screened under the National Newborn Screening program in Greece. In cases where newborn screening is unavailable, and symptoms are present, a clinical physician will conduct a more comprehensive evaluation, including the measurement of total and free carnitines in the blood, as well as determining the acylcarnitine profile in plasma. The diagnosis is confirmed through appropriate genetic testing3<\/sup>.<\/p>\n

            The management of LC-FAODs is symptomatic and includes avoiding fasting, preventing acute metabolic crises, and implementing a specialized, personalized medical diet4<\/sup>.<\/p>\n

            Sources<\/span><\/p>\n

              \n
            1. Rinaldo P, Matern D, Bennett MJ ,Annu, Rev Physiol. 2002;64:477.<\/li>\n
            2. Marsden D, Bedrosian CL, Vockley J, Genet Med. 2021;23(5):816.<\/li>\n
            3. Merritt JL 2nd, Vedal S, Abdenur JE, Au SM, Barshop BA, Feuchtbaum L, Harding CO, Hermerath C, Lorey F, Sesser DE, Thompson JD, Yu A, Mol Genet Metab. 2014;111(4):484.<\/li>\n
            4. Joshua J Baker, Barbara K Burton, touchREV Endocrinol. 2021 Nov; 17(2): 108\u2013111<\/li>\n<\/ol>\n

              <\/div>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

              [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” rt_padding_left=”0″ rt_padding_right=”90px” class=”small_row” rt_padding_top=”10″][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_padding_left=”0″][vc_column_text]<\/p>\n\n\n\n\n
              Alagille<\/span><\/td>\n<\/tr>\n
              \"\"<\/td>\n\n
              Syndrome (ALGS)<\/strong><\/div>\n

               <\/p>\n

              Alagille Syndrome is a rare genetic disorder with an incidence of 1:30,000-50,0001<\/sup>. It is an autosomal dominant condition, meaning that children of a patient with Alagille Syndrome have a 50% chance of being affected.<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nRead More<\/a><\/span>\n
              \n
              \n

              Alagille Syndrome is caused by mutations in certain genes (JAG1 or NOTCH2), resulting in defective bile duct formation within the liver and abnormalities in skeletal, ocular, cardiovascular, and renal development2<\/sup>. The lack of bile ducts, a hallmark of ALGS, leads to reduced bile flow, accumulation of bile acids, and cholestatic liver damage.<\/p>\n

              Around 40% of patients inherit the mutation from their parents, while 60% have de novo mutations3<\/sup>.<\/p>\n

              Symptoms of Alagille Syndrome appear at birth and include jaundiced skin and intense itching4,5<\/sup>. The cholestatic itching caused by ALGS is the most severe of any liver disease6<\/sup>. Other symptoms involve various systems, such as the skeletal system (Butterfly vertebrae, characteristic facial features with a prominent forehead, deep-set eyes, and a pointed chin), the cardiovascular system (pulmonary stenosis, Tetralogy of Fallot), hearing loss, ocular disorders (posterior embryotoxon), and renal issues (dysplasia, renal tubular acidosis)1,5,7<\/sup>. Xanthomas (fat deposits on extending surfaces resulting from increased cholesterol) also affect 30-42% of patients5,8<\/sup>.<\/p>\n

              When Alagille Syndrome is suspected in a newborn or infant with cholestasis, jaundice, and morphological or other clinical findings, a comprehensive laboratory evaluation is performed to confirm the diagnosis. If the diagnosis is not established, but clinical findings suggest ALGS, the patient may undergo genetic testing3,8<\/sup>.<\/p>\n

              Diagnosing ALGS is challenging due to the fact that its symptoms could be attributed to other equally rare diseases, such as intrahepatic cholestasis or progressive familial intrahepatic cholestasis. Unnecessary surgery could worsen the course of the disease9<\/sup>.<\/p>\n

              ALGS leads to progressive liver failure, with 24% – 42% of patients surviving without liver transplantation up to the age of 18.510<\/sup> years. Cardiovascular complications are a significant cause of morbidity and mortality not only in children but also in adult patients with ALGS, who need to be identified and managed as early as possible.<\/p>\n

              ALGS is a multisystem disorder that requires an interdisciplinary team of specialized pediatricians and pathologists for effective management and ensuring long-term survival along with a good quality of life for these fragile patients11<\/sup>.<\/p>\n

                \n
              1. Eur J Hum Genet 2014; 22.<\/li>\n
              2. J Hepatol 2016; 65:631\u2013642.<\/li>\n
              3. Diagnostics 2020; 10:907\u2013924.<\/li>\n
              4. Med Sci Monit 2014; 20:476\u2013480;<\/li>\n
              5. J Pediatr Gastroenterol Nutr 2018; 67:148\u2013156;<\/li>\n
              6. J Pediatr Gastroenterol Nutr 2010; 51:759\u2013765;<\/li>\n
              7. Eur J Hum Genet 2012; 20:251\u2013257.<\/li>\n
              8. Appl Clin Genet 2016;9:75-82<\/li>\n
              9. International Liver Congress (EASL), 2020<\/li>\n
              10. Kamath BM, et al. Hepatol Comms 2020; 4:387\u2013398.<\/li>\n
              11. J Multidiscip Healthc. 2022; 15: 353\u2013364.<\/li>\n<\/ol>\n<\/div>\n

                <\/div>
                \n[\/vc_column_text][vc_column_text]<\/p>\n\n\n\n\n\n
                \"\"<\/td>\n<\/tr>\n
                Alagille<\/td>\n<\/tr>\n
                <\/td>\n\n
                Syndrome (ALGS)<\/strong><\/div>\n

                 <\/p>\n

                \n

                Alagille Syndrome is a rare genetic disorder with an incidence of 1:30,000-50,0001<\/sup>. It is an autosomal dominant condition, meaning that children of a patient with Alagille Syndrome have a 50% chance of being affected.<\/p>\nRead More<\/a><\/span>\n


                \nAlagille Syndrome is caused by mutations in certain genes (JAG1 or NOTCH2), resulting in defective bile duct formation within the liver and abnormalities in skeletal, ocular, cardiovascular, and renal development2<\/sup>. The lack of bile ducts, a hallmark of ALGS, leads to reduced bile flow, accumulation of bile acids, and cholestatic liver damage.<\/p>\n

                Around 40% of patients inherit the mutation from their parents, while 60% have de novo mutations3<\/sup>.<\/p>\n

                Symptoms of Alagille Syndrome appear at birth and include jaundiced skin and intense itching4,5<\/sup>. The cholestatic itching caused by ALGS is the most severe of any liver disease6<\/sup>. Other symptoms involve various systems, such as the skeletal system (Butterfly vertebrae, characteristic facial features with a prominent forehead, deep-set eyes, and a pointed chin), the cardiovascular system (pulmonary stenosis, Tetralogy of Fallot), hearing loss, ocular disorders (posterior embryotoxon), and renal issues (dysplasia, renal tubular acidosis)1,5,7<\/sup>. Xanthomas (fat deposits on extending surfaces resulting from increased cholesterol) also affect 30-42% of patients5,8<\/sup>.<\/p>\n

                When Alagille Syndrome is suspected in a newborn or infant with cholestasis, jaundice, and morphological or other clinical findings, a comprehensive laboratory evaluation is performed to confirm the diagnosis. If the diagnosis is not established, but clinical findings suggest ALGS, the patient may undergo genetic testing3,8<\/sup>.<\/p>\n

                Diagnosing ALGS is challenging due to the fact that its symptoms could be attributed to other equally rare diseases, such as intrahepatic cholestasis or progressive familial intrahepatic cholestasis. Unnecessary surgery could worsen the course of the disease9<\/sup>.<\/p>\n

                ALGS leads to progressive liver failure, with 24% – 42% of patients surviving without liver transplantation up to the age of 18.510<\/sup> years. Cardiovascular complications are a significant cause of morbidity and mortality not only in children but also in adult patients with ALGS, who need to be identified and managed as early as possible.<\/p>\n

                ALGS is a multisystem disorder that requires an interdisciplinary team of specialized pediatricians and pathologists for effective management and ensuring long-term survival along with a good quality of life for these fragile patients11<\/sup>.<\/p>\n

                  \n
                1. Eur J Hum Genet 2014; 22.<\/li>\n
                2. J Hepatol 2016; 65:631\u2013642.<\/li>\n
                3. Diagnostics 2020; 10:907\u2013924.<\/li>\n
                4. Med Sci Monit 2014; 20:476\u2013480;<\/li>\n
                5. J Pediatr Gastroenterol Nutr 2018; 67:148\u2013156;<\/li>\n
                6. J Pediatr Gastroenterol Nutr 2010; 51:759\u2013765;<\/li>\n
                7. Eur J Hum Genet 2012; 20:251\u2013257.<\/li>\n
                8. Appl Clin Genet 2016;9:75-82<\/li>\n
                9. International Liver Congress (EASL), 2020<\/li>\n
                10. Kamath BM, et al. Hepatol Comms 2020; 4:387\u2013398.<\/li>\n
                11. J Multidiscip Healthc. 2022; 15: 353\u2013364.<\/li>\n<\/ol>\n

                  <\/div>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

                  [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row”][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_padding_left=”0″][vc_column_text]<\/p>\n\n\n\n\n
                  <\/td>\n<\/td>\n<\/tr>\n
                  \n
                  Wilson’s
                  \nDisease<\/strong><\/div>\n

                   <\/p>\n

                  Wilson’s Disease (WD), formerly known as hepatolenticular degeneration, is a rare inherited genetic disorder, inherited in an autosomal recessive manner.<\/div>\n<\/td>\n
                  		\"\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nRead More<\/a><\/span>\n
                  \n
                  \n

                  It is caused by mutations in the ATP7B gene, which encodes a transmembrane copper transport protein, disrupting its function and leading to the accumulation of copper in the liver, brain, and other vital organs.1<\/sup><\/p>\n

                  The usual age of onset is between 4-40 years, although cases as young as 3 years and as old as 70 years have been reported in the literature2<\/sup><\/p>\n

                  The clinical course can vary in terms of the type and severity of symptoms, but progressive liver disease is a common feature. Patients may also present with neurological and psychiatric symptoms, as well as ophthalmological manifestations such as Kayser-Fleischer rings.<\/p>\n

                  Guidelines recommend that in any patient with unexplained liver function abnormalities, especially when associated with neurological or psychiatric disorders, the possibility of Wilson’s disease should be considered.3<\/sup><\/p>\n

                  If the diagnosis is confirmed, treatment is lifelong.<\/p>\n

                  Sources<\/span><\/p>\n

                    \n
                  1. Cz\u0142onkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML. Wilson disease. Nat Rev Dis Primers. 2018 Sep 6;4(1):21. doi: 10.1038\/s41572-018-0018-3. PMID: 30190489; PMCID: PMC6416051<\/li>\n
                  2. Alkhouri N, Gonzalez-Peralta RP, Medici V. Wilson disease: a summary of the updated AASLD Practice Guidance. Hepatol Commun. 2023 May 15;7(6):e0150. doi: 10.1097\/HC9.0000000000000150. PMID: 37184530; PMCID: PMC10187853<\/li>\n
                  3. Schilsky ML, Roberts EA, Bronstein JM, Dhawan A, Hamilton JP, Rivard AM, Washington MK, Weiss KH, Zimbrean PC. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2022 Dec 7. doi: 10.1002\/hep.32801. Epub ahead of print. PMID: 36151586.<\/li>\n<\/ol>\n<\/div>\n

                    <\/div>[\/vc_column_text][vc_column_text]<\/p>\n\n\n\n\n\n
                    \"\"<\/td>\n<\/tr>\n
                    \n
                    Wilson’s Disease<\/strong><\/div>\n<\/td>\n<\/tr>\n
                    <\/td>\n\n
                    \n

                    Wilson’s Disease (WD), formerly known as hepatolenticular degeneration, is a rare inherited genetic disorder, inherited in an autosomal recessive manner.<\/p>\nRead More<\/a><\/span>\n


                    \nIt is caused by mutations in the ATP7B gene, which encodes a transmembrane copper transport protein, disrupting its function and leading to the accumulation of copper in the liver, brain, and other vital organs.1<\/sup><\/p>\n

                    The usual age of onset is between 4-40 years, although cases as young as 3 years and as old as 70 years have been reported in the literature. 2<\/sup><\/p>\n

                    The clinical course can vary in terms of the type and severity of symptoms, but progressive liver disease is a common feature. Patients may also present with neurological and psychiatric symptoms, as well as ophthalmological manifestations such as Kayser-Fleischer rings.<\/p>\n

                    Guidelines recommend that in any patient with unexplained liver function abnormalities, especially when associated with neurological or psychiatric disorders, the possibility of Wilson’s disease should be considered.3<\/sup><\/p>\n

                    If the diagnosis is confirmed, treatment is lifelong.<\/p>\n

                    Sources<\/span><\/p>\n

                      \n
                    1. Cz\u0142onkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML. Wilson disease. Nat Rev Dis Primers. 2018 Sep 6;4(1):21. doi: 10.1038\/s41572-018-0018-3. PMID: 30190489; PMCID: PMC6416051<\/li>\n
                    2. Alkhouri N, Gonzalez-Peralta RP, Medici V. Wilson disease: a summary of the updated AASLD Practice Guidance. Hepatol Commun. 2023 May 15;7(6):e0150. doi: 10.1097\/HC9.0000000000000150. PMID: 37184530; PMCID: PMC10187853<\/li>\n
                    3. Schilsky ML, Roberts EA, Bronstein JM, Dhawan A, Hamilton JP, Rivard AM, Washington MK, Weiss KH, Zimbrean PC. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2022 Dec 7. doi: 10.1002\/hep.32801. Epub ahead of print. PMID: 36151586.<\/li>\n<\/ol>\n

                      <\/div>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

                      [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row” rt_padding_top=”0″][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll”][vc_column_text]<\/p>\n\n\n\n\n
                      Congenital<\/td>\n<\/tr>\n
                      <\/td>\n\n
                      Adrenal<\/strong>
                      \nHyperplasia<\/strong><\/div>\n

                       <\/p>\n

                      \n

                      Congenital Adrenal Hyperplasia (CAH) comprises a group of disorders resulting from the deficiency of one of the enzymes involved in the synthesis of cortisol, a hormone produced in the adrenal glands. CAH is inherited in an autosomal recessive manner1<\/sup>.<\/p>\nRead More<\/a><\/span>\n


                      \nThe deficiency of cortisol leads to an increase in ACTH (adrenocorticotropic hormone), which is secreted by the pituitary gland. This, in turn, results in the hyperplasia (overgrowth) of the adrenal glands, leading to a wide range of clinical manifestations2<\/sup>.<\/p>\n

                      The most common cause of CAH is a deficiency in the 21-hydroxylase enzyme, which is present in approximately 90% of cases3<\/sup>.<\/p>\n

                      Conventionally, the deficiency of the 21-hydroxylase enzyme is classified into classical and non-classical forms. The classical form can be further categorized into “salt-wasting” and “simple virilizing” subtypes4<\/sup>.<\/p>\n

                      The clinical symptoms of the disease depend on the type of CAH, the severity of the enzyme deficiency, and the gender of the patient. Patients with salt-wasting CAH typically present from neonatal or early infancy with symptoms like poor weight gain, vomiting, dehydration, and hyperkalemia. Female individuals with CAH may exhibit ambiguous genitalia or virilization, even prenatally, due to their exposure to high levels of adrenal androgens caused by adrenal gland hyperplasia. Other symptoms may include growth delay, delayed puberty, infertility, hirsutism, and features of a metabolic syndrome.5,6<\/sup><\/p>\n

                      Diagnosis of CAH can be made at birth by implementing newborn screening for metabolic disorders in a private context. At present, testing for CAH is not included in the diseases screened in national Newborn Screening Programs. In cases where newborn screening is not available and there are clinical findings suggestive of CAH, measurements of 17-hydroxyprogesterone, which are typically very high immediately after birth, especially in the classical form of 21-hydroxylase deficiency, may be conducted. As part of the evaluation, serum electrolyte measurements, other hormone assays to identify the specific enzyme deficiency, and, if necessary, a cosyntropin stimulation test (ACTH stimulation test) may be performed. Genetic testing is not always deemed necessary for diagnosis, except when the results of the other testing methods are inconclusive or if genetic counseling is needed7<\/sup>.<\/p>\n

                      The management of CAH includes achieving three primary clinical objectives: the replacement of cortisol (and aldosterone if required), reducing exposure to high levels of adrenal androgens based on the patient’s age and gender, and avoiding overtreatment with its associated complications8<\/sup>.<\/p>\n

                      Sources<\/span><\/p>\n

                        \n
                      1. J Clin Endocrinol Metab, March 2008, 93(3):653\u2013 660.<\/li>\n
                      2. J Steroid Biochem Mol Biol. 2015 Sep; 153: 63\u201371.<\/li>\n
                      3. N Engl J Med.2003;349:776\u2013788.<\/li>\n
                      4. Endocrinol Metab Clin North Am. 2015 Jun; 44(2): 275\u2013296.<\/li>\n
                      5. Seminars in reproductive medicine. 2012 Oct;30(5):400\u2013409.<\/li>\n
                      6. J Clin Endocrinol Metab. 2010 Nov; 95(11): 5110\u20135121.<\/li>\n
                      7. Eur J Hum Genet. 2020;28(10):1341.<\/li>\n
                      8. J. Clin. Endocrinol. Metab. 2013, 98, 2645\u20132655.<\/li>\n<\/ol>\n

                        <\/div>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

                        [\/vc_column_text][\/vc_column][\/vc_row][vc_row rt_row_background_width=”fullwidth” rt_row_content_width=”default” rt_row_style=”default-style” rt_row_borders=”” rt_row_paddings=”true” rt_bg_effect=”classic” rt_bg_image_repeat=”repeat” rt_bg_size=”cover” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_bg_video_format=”self-hosted” class=”small_row”][vc_column rt_wrp_col_paddings=”false” rt_border_top=”” rt_border_bottom=”” rt_border_left=”” rt_border_right=”” rt_border_top_mobile=”” rt_border_bottom_mobile=”” rt_border_left_mobile=”” rt_border_right_mobile=”” rt_bg_image_repeat=”repeat” rt_bg_size=”auto auto” rt_bg_position=”right top” rt_bg_attachment=”scroll” rt_padding_left=”0″][vc_column_text]<\/p>\n\n\n\n\n
                        Adrenal<\/span><\/td>\n<\/tr>\n
                        \"\"<\/td>\n\n
                        Insufficiency<\/strong><\/div>\n

                         <\/p>\n

                        Adrenal insufficiency is a rare condition that can develop over time and, less commonly, can present as an acute, potentially life-threatening condition called an adrenal crisis. The most common cause of adrenal insufficiency is the abrupt discontinuation of corticosteroid therapy after prolonged treatment.<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nRead More<\/a><\/span>\n
                        \n
                        \n

                        It is classified into:<\/p>\n