The clinical presentation of children with Wolman disease can vary from an early presentation on the first day of birth with abdominal swelling, vomiting, fatty stools to presenting weeks or months later with a failure to thrive [25] [26]. Life expectancy is usually less than one year with mortality mainly caused by complications of the disease in the liver, small intestine and the adrenal glands.

Due to the pathophysiology of the illness, there is a buildup of cholesteryl esters and triglycerides in several body tissues and organs. Accumulations in the liver and spleen may cause hepatomegaly and splenomegaly, possibly leading to liver failure. Similarly, a buildup of these substances in the intestines affects intestinal absorption, thus leading to severe weight loss [27]. In the adrenals, the disease can lead to adrenocortical insufficiency.

• Splenomegaly

  Abdominal distention may be present because of hepatomegaly, splenomegaly and generalized lymphadenopathy 2. The underlying biochemical abnormality is a deficiency of acid lipase/acid esterase. [radiopaedia.org]

  Figure 8 Coronal CT section of abdomen showing fatty liver, splenomegaly, low attenuation mesenteric lymph nodes and ascites. Figure 9 Axial CT section of abdomen showing low attenuation fatty lymph nodes, splenomegaly and ascites. [casereports.bmj.com]

  Other signs often include splenomegaly, high total cholesterol and LDL-cholesterol, elevated triglycerides, and low HDL-cholesterol. The diagnosis of LAL deficiency requires clinical experience and specialized laboratory tests. [ncbi.nlm.nih.gov]

  Hepatomegaly, splenomegaly, and lymphadenopathy are also visible on computed tomography (CT) and magnetic resonance imaging (MRI). They may also show calcifications in the enlarged adrenal glands. [symptoma.com]

• Anemia

  The complete deficiency of LAL is responsible of Wolman disease (WD), a severe systemic disease manifesting in the first days of life with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, jaundice, anemia, and thrombocytopenia. [ncbi.nlm.nih.gov]

  Peripheral blood showed macrocytic anemia with mild neutropenia, thrombocytopenia, and acanthocytes. Approximately 20% of lymphocytes demonstrated between 1 and 7 cytoplasmic vacuoles (panels A-C; May–Grünwald–Giemsa stain). [imagebank.hematology.org]

  […] hepatosplenomegaly), poor weight gain, a yellowish color of the skin and the whites of the eyes (jaundice), vomiting, diarrhea, fatty stool (steatorrhea), and poor absorption of nutrients from food (malabsorption), as well as calcium deposits in adrenal glands, anemia [jewishgeneticdiseases.org]

  These may include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, low muscle tone, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, developmental delay, low amounts of iron in the blood (anemia) [smpdb.ca]

  ✔ Refractory Anemia with Ringed Sideroblasts (Sideroblastic anemia) ✔ Refractory Anemia with Excess Blasts ✔ Refractory Anemia with Excess Blasts in Transformation ✔ Chronic Myelomonocytic Leukemia (CMML) ✔ Lymphoma is a cancer of the leukocytes that [parentsguidecordblood.org]

• Weight Loss

  Similarly, a buildup of these substances in the intestines affects intestinal absorption, thus leading to severe weight loss. In the adrenals, the disease can lead to adrenocortical insufficiency. [symptoma.com]

  loss, ascites, and hepatosplenomegaly. [imagebank.hematology.org]

  Severe chronic diarrhea and weight loss in cholesteryl ester storage disease: A case report. [ncbi.nlm.nih.gov]

  […] or sometimes even weight loss Hardening of the glands above the kidneys (adrenal glands) Causes LAL Deficiency is a genetic condition, which means is it caused by our genes. [checkorphan.org]

  loss and loss of muscle mass (cachexia or inanition). [clinicaltrials.gov]

• Developmental Delay

  These may include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, low muscle tone, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, developmental delay, low amounts of iron in the blood (anemia) [smpdb.ca]

  Examination revealed pale child having firm and nontender hepatosplenomegaly (Liver: 8 cm below right costal margin and spleen: 5 cm in long axis) with no lymphadenopathy or developmental delay. [casereports.in]

  Common symptoms in infants include enlarged liver and spleen, poor weight gain, low muscle tone, jaundice, vomiting, diarrhea, developmental delay, anemia, and poor absorption of nutrients from food. [diseaseinfosearch.org]

  Potential symptoms include enlarged liver or spleen, vomiting, jaundice, anemia, diarrhea, little or no weight gain, poor muscle tone, developmental delays, and poor absorption of nutrients from food. [disabled-world.com]

• Weakness

  WD often get progressively worse eventually leading to life-threatening complications during infancy including extremely low levels of circulating red blood cells (severe anemia), hepatic dysfunction or failure, and physical wasting away and severe weakness [clinicaltrials.gov]

  […] often become progressively worse, eventually leading to life-threatening complications during infancy including extremely low levels of circulating red blood cells (severe anemia), hepatic dysfunction or failure, and physical wasting away and severe weakness [centogene.com]

  Characteristic features include muscle weakness, loss of muscle coordination ( ataxia ) and other problems with movement, speech problems, and mental illness. [en.wikipedia.org]

  Additionally, the heart rhythm problems associated with Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe [ghr.nlm.nih.gov]

  […] often get progressively worse eventually leading to life-threatening complications during infancy including extremely low levels of circulating red blood cells (severe anemia), liver (hepatic) dysfunction or failure, and physical wasting away and severe weakness [rarediseases.org]

• Death in Infancy

  […] in infancy ensuing (usually within 6 months). [radiopaedia.org]

  Wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. [ncbi.nlm.nih.gov]

  It presents with vomiting, diarrhea, poor weight gain, and hepatomegaly subsequently leading to death in infancy. Definite diagnosis is based on genetic confirmation by the LIPA gene sequencing. [go.gale.com]

• Dyspnea

  Symptoms of WPW may include one or more of the following: Heart palpitations – a sudden pounding, fluttering or Racing feeling in your chest Dizziness – feeling lightheaded or faint Shortness of breath (dyspnea) Anxiety Rarely, cardiac arrest (sudden [my.clevelandclinic.org]

  A variety of symptoms may occur during these episodes including palpitations, difficulty breathing (dyspnea), light-headedness, chest pain, decreased exercise tolerance, anxiety, and dizziness. [rarediseases.org]

• Vomiting

  Case Report A two month old full term female baby born of non-consanguineous marriage, presented with history of repeated diarrhea, vomiting, progressive abdominal distension and shortness of breath since last three weeks. [casereports.in]

  Patients with Wolman disease typically present during the first two months of life with failure to thrive, diarrhea and vomiting. Abdominal distention may be present because of hepatomegaly, splenomegaly and generalized lymphadenopathy 2. [radiopaedia.org]

  Symptoms may include hepatosplenomegaly, liver disease (cirrhosis), and malabsorption with diarrhea, vomiting, and steatorrhea. For detailed information about this disease visit : National Institutes of Health (NIH) > Carrier Frequency by Ethnicity > [jewishgeneticdiseases.org]

  In early onset LAL deficiency, clinical manifestations start in the first few weeks of life with persistent vomiting, failure to thrive, hepatosplenomegaly, liver dysfunction and hepatic failure. [casereports.bmj.com]

• Diarrhea

  Diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. Liver function is normal. [ncbi.nlm.nih.gov]

  Patients with Wolman disease typically present during the first two months of life with failure to thrive, diarrhea and vomiting. Abdominal distention may be present because of hepatomegaly, splenomegaly and generalized lymphadenopathy 2. [radiopaedia.org]

  Case Report A two month old full term female baby born of non-consanguineous marriage, presented with history of repeated diarrhea, vomiting, progressive abdominal distension and shortness of breath since last three weeks. [casereports.in]

  Symptoms may include hepatosplenomegaly, liver disease (cirrhosis), and malabsorption with diarrhea, vomiting, and steatorrhea. For detailed information about this disease visit : National Institutes of Health (NIH) > Carrier Frequency by Ethnicity > [jewishgeneticdiseases.org]

• Failure to Thrive

  Patients with Wolman disease typically present during the first two months of life with failure to thrive, diarrhea and vomiting. Abdominal distention may be present because of hepatomegaly, splenomegaly and generalized lymphadenopathy 2. [radiopaedia.org]

  In infants, poor weight gain, massive hepatosplenomegaly, calcified adrenal glands (present about 2/3 of the time), vomiting, diarrhea and failure to thrive are indicative of Wolman disease. The clinical picture is more variable in CESD. [ncbi.nlm.nih.gov]

  In early onset LAL deficiency, clinical manifestations start in the first few weeks of life with persistent vomiting, failure to thrive, hepatosplenomegaly, liver dysfunction and hepatic failure. [casereports.bmj.com]

• Abdominal Distension

  Hepatosplenomegaly, steatorrhea, abdominal distension, severe malabsorption and resultant malnutrition, and adrenal calcification are evident within the first months postpartum. [ommbid.mhmedical.com]

  Affected infants show signs of lipid storage in most tissues, including hepatosplenomegaly, abdominal distension, vomiting, steatorrhea, failure to thrive, and adrenal calcifications. [ncbi.nlm.nih.gov]

  Wolman disease is characterized by neonatal abdominal distension, major or even massive hepatosplenomegaly and calcified adrenal glands, cholesteryl ester storage disease presents with microvesicular steatosis leading to hepatomegaly and hypercholesterolaemia [orpha.net]

  distension and failure to thrive. [casereports.bmj.com]

• Nausea

  The most common side effects which occurred in patients treated with Kanuma during the trial were diarrhea, vomiting, fever, anemia, cough, constipation, and nausea. [copybook.com]

  […] these symptoms Abdominal distention Abdominal bloating Abdominal swelling Belly bloating Bloating [ more ] 0003270 Adrenal calcification 0010512 Global developmental delay 0001263 Hepatic failure Liver failure 0001399 Hepatomegaly Enlarged liver 0002240 Nausea [rarediseases.info.nih.gov]

  The most commonly reported side effects in children and adults include headache, fever, inflammation of the throat and nasal passages, constipation, and nausea. [liverfoundation.org]

• Heart Disease

  disease［风湿性心脏病］ •multivalve disease［多瓣膜病］ •valvular heart disease［心瓣膜病］ •mitral(aortic, pulmonary, tricuspid) stenosis［二尖瓣（主动脉瓣，肺动肪瓣，三尖瓣）狭窄］ •mitral (aortic, tricuspid) regurgitation(insufficiency)［二尖瓣（主动脉瓣，三尖瓣）反流（关闭不全）］ •coronary artery (heart) disease [a-hospital.com]

  Eight patients (31%) had structural heart disease, 9 patients had a pre-excitation syndrome, and the other 17 children had a concealed accessory atrioventricular pathway. [dict.cnki.net]

  Wolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. [ghr.nlm.nih.gov]

  An accessory pathway is present from birth and WPW syndrome is most common in babies born with other types of heart defects (congenital heart disease). However, it’s also seen in people who have structurally normal hearts. [bhf.org.uk]

  The syndrome also is associated with some forms of congenital heart disease, such as Ebstein's anomaly. Otherwise, little is known about why the extra pathway develops. WPW is more common in males than in females. [mayoclinic.org]

• Hepatosplenomegaly

  Wolman’s disease usually manifests in the first year of life with failure to thrive, relentless vomiting and hepatosplenomegaly. Calcification of the adrenals, foamy macrophages, hepatosplenomegaly is pathognomic for the disease [3]. [casereports.in]

  Plain radiograph bilateral calcification of the adrenal glands, which are enlarged 2,4 CT may show hepatosplenomegaly (with fatty liver) bilaterally enlarged calcified (punctate calcification) adrenal glands that retain their normal triangular shapes [radiopaedia.org]

  Gaucher disease ( GBA mutations): overlapping clinical features of lysosomal acid lipase deficiency and Gaucher disease are hepatosplenomegaly and thrombocytopenia. [bredagenetics.com]

  Infant leukemia most commonly present with pallor and hepatosplenomegaly. [ncbi.nlm.nih.gov]

  Hepatosplenomegaly, steatorrhea, abdominal distension, severe malabsorption and resultant malnutrition, and adrenal calcification are evident within the first months postpartum. [ommbid.mhmedical.com]

• Hepatomegaly

  Massive hepatomegaly and hepatic fibrosis may lead to esophageal varices. Patients with CESD may be at risk of developing pulmonary hypertension. [bredagenetics.com]

  hepatomegaly and abdominal distension/failure to thrive/elevated transaminases are currently underway. [ncbi.nlm.nih.gov]

  Isolated hepatomegaly and a hypercholesterolemia IIb pattern can be the presenting signs. Hepatic fibrosis with unpredictable progression to frank cirrhosis can occur. Premature atherosclerosis may be severe. [ommbid.mhmedical.com]

  Abdominal distention may be present because of hepatomegaly, splenomegaly and generalized lymphadenopathy 2. The underlying biochemical abnormality is a deficiency of acid lipase/acid esterase. [radiopaedia.org]

  Cholesteryl ester storage disease and Wolman disease are sphingolipidoses, an inherited disorder of metabolism, caused by lysosomal acid lipase deficiency resulting in hyperlipidemia and hepatomegaly. [merckmanuals.com]

• Jaundice

  The complete deficiency of LAL is responsible of Wolman disease (WD), a severe systemic disease manifesting in the first days of life with vomiting, diarrhea, failure to thrive, hepatosplenomegaly, jaundice, anemia, and thrombocytopenia. [ncbi.nlm.nih.gov]

  Rat fever (leptospirosis) can also cause jaundice due to the liver. In jaundice due to the liver, there is invariably cholestasis. [en.wikipedia.org]

  Symptoms include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, a yellowish color of the skin and the whites of the eyes (jaundice), vomiting, diarrhea, fatty stool (steatorrhea), and poor absorption of nutrients from food (malabsorption [jewishgeneticdiseases.org]

  Other symptoms that can develop in children include: Jaundice Calcium deposits in the adrenal glands, which causes them to harden The onset of CESD varies, and in some cases the disorder may not be diagnosed until the child reaches adulthood. [medic8.com]

  These may include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, low muscle tone, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, developmental delay, low amounts of iron in the blood (anemia) [smpdb.ca]

• Scleral Icterus

  The presence of scleral icterus indicates a serum bilirubin of at least 3 mg/dL. The conjunctiva of the eye are one of the first tissues to change color as bilirubin levels rise in jaundice. This is sometimes referred to as scleral icterus. [en.wikipedia.org]

The laboratory diagnosis of Wolman disease is based on the confirmation of a deficient LAL in the white blood cells or dermal fibroblasts.

The characteristic finding on imaging is normally shaped but bilaterally enlarged adrenal glands with pathognomonic calcifications outlining the cortex. Differential diagnoses of adrenal calcification in children include neuroblastoma and adrenal hemorrhage, though they differ in their pattern of calcification.

Hepatomegaly, splenomegaly, and lymphadenopathy are also visible on computed tomography (CT) and magnetic resonance imaging (MRI). They may also show calcifications in the enlarged adrenal glands. Likewise, abdominal ultrasound can be used to examine abdominal viscera [28].

Management of WD is mainly symptomatic with no definitive treatment options available. Bone marrow and umbilical cord blood transplants are promising treatment interventions. However, the lack of matched donors and the severe, fast wasting seen in affected individuals limit the therapeutic efficacy of bone marrow transplantation [5] [6].

There are few therapeutic measures in CESD with the target to attenuate consequences of LAL-D. Research involving LAL enzyme replacement therapy for definitive management is currently underway.

Lipid-lowering therapies

The use of HMG-CoA reductase inhibitors (statins) in lowering lipid levels in patients with CESD has had mixed results with some reports of success and some reported persistence of dyslipidemia [14] [20] [29]. Although a decrease in liver size has been seen in some patients treated with HMG-CoA inhibitors [15] [30], liver fibrosis has continued in these patients [19] [31]. Similarly, some evidence is available on the protective benefits of HMG-CoA inhibitors on the heart, but liver damage still progressed in these patients with some ending up with liver failure [15] [19].

In a 15-year-old test subject with CESD, six months of therapy on a cholesterol absorption inhibitor (Ezetimibe) was able to bring liver transaminases to normal and decrease total cholesterol and LDL-levels, as well as reduce cytokines and oxidative stress parameters measured in the serum [32]. Ezetimibe may thus, be of benefit in certain cases.

Hematopoietic stem cell and liver transplantation

Although there is inadequate data on long-term outcomes, liver transplant in WD patients with liver failure has improved survival in a few patients for up to 5 years [19] [33] [34]. Similarly, hematopoietic stem cell transplantation has been studied in some patients with WD, but problems related to their toxicity and the multi-organ nature of the disease have limited the efficacy of this therapy [35] [36] [37] [38].

Enzyme replacement therapy

Enzyme replacement therapy aims to replace the deficient lysosomal acid lipase enzyme in LAL-D patients.

Sebelipase alfa, a human recombinant LAL enzyme, is currently undergoing clinical testing with promising results regarding an improvement of liver function test values, reducing the accumulation of cholesteryl esters in the lysosomes of cells and an absence of severe side effects to therapy [39] [40].

The prognosis of WD patients is generally very poor and characterized with a life expectancy of less than one year. The quality of life of CESD patients tends to be diverse based on the broad spectrum of clinical presentations. No evidence-based quality of life scales are available at present. The clinical manifestations of the disease can vary from unnoticed signs and symptoms to very severe features with some infants having an early liver failure and requiring transplantation, while others may have a stroke, aneurysm or coronary artery disease [19] [20] [21] [22] [23] [24].

Wolman disease is an inherited disorder passed down by autosomal recessive inheritance. The inherited defective gene in WD is lysosomal acid lipase gene (LIPA). The LIPA gene is responsible for the synthesis of lysosomal acid lipase enzyme which is a highly important part of the metabolism of cholesterol and triglycerides. The abnormality in the LIPA gene, therefore, leads to a deficiency and/or defective lysosomal acid lipase enzyme production leading to a massive buildup of unmetabolized cholesterol and triglycerides in the body. These fats end up in tissues and organs of the body causing various degrees of damage. There is a less severe manifestation of lysosomal acid lipase deficiency named

There is a less severe manifestation of lysosomal acid lipase deficiency named cholesteryl ester storage disease (CESD).

Wolman disease is estimated to occur in less than 1 per 300,000 live births although the actual incidence remains uncertain [1] [8]. Studies in some populations, like the Iranian Jews in Los Angeles have shown incidence rates of 1 in 4200 births; however, this study population is too insulated to be representative [9].

Neutral lipids like cholesteryl esters and triglycerides derived from LDL are metabolized by LAL in the lysosomes of cells. The byproducts of this metabolism (fatty acids and free cholesterol) or the neutral lipids themselves directly modulate the expression of genes responsible for the production/uptake of cholesterol and lipogenesis through their interaction with transcription factors named sterol regulatory element-binding proteins (SREBPs) [2] [10]. Physiologically, an unusually high amount of cholesterol acts via SREBP-2 to decrease cellular uptake of cholesterol (by downregulation of LDL receptors), reduce cholesterol synthesis (by inhibiting hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase) and increase cholesterol esterification through acyl-cholesterol acyltransferase. Similarly, high fatty acids in cells act via SREBP-1c to reduce fatty acid production through reduction in triglyceride and phospholipid synthesis [11].

In response to a lack of intracellular free cholesterol caused by the inability of LAL to break down cholesteryl esters and triglycerides, SREBP-2 senses this deficiency of free cholesterol and ramps up the production of HMG-CoA reductase, leading to increased levels of free cholesterol inside the cell [12]. SREBP in this free cholesterol deficiency scenario also causes increased endocytosis by the LDL receptors and enhanced production of apolipoprotein B (ApoB) and very-low-density lipoprotein cholesterol (VLDL-C) [12].

It is speculated that the HMG-CoA reductase induced a rise in free cholesterol level in lysosomal acid lipase deficiency (LAL-D) causes a reduction in LDL-C clearance and inhibition of LDL receptor action. Cholesterol movement in LAL-D, however, appears to be different. In what could be a significant cause of hypercholesterolemia in LAL-D, a high VLDL-C synthesis (the natural export mechanism for cholesterol from hepatocytes) has been observed in response to high cholesterol production and this further leads to increased LDL-C synthesis [13].

The lipid profile of LAL-D patients shows derangements in all the components of the panel with raised total cholesterol and TGs caused by the buildup of ApoB lipoproteins like VLDL-C and LDL-C. Low HDL-C may be possibly caused by reduced adenosine triphosphate-binding cassette transporter A1 (ABCA1) which leads to decreased synthesis of mature α-HDL particles [14] [15]. Normally, high cellular cholesterol acts via oxysterol to stimulate this ABCA1 gene. In LAL-D with its attendant low intracellular free cholesterol (due to accumulation of cholesteryl esters within lysosomes), the reverse is the case with reduced oxysterol-dependent activation of ABCA1. This reduced action of ABCA1 leads to reduced synthesis of α-HDL particles by affecting the cholesterol-dependent, ABCA1-mediated transfer of cholesterol to the extracellular lipid-poor apolipoprotein A1 (ApoA-I), an important step in the α-HDL particles synthesis [16] [17]. Evidence for these processes has been demonstrated in experiments where the introduction of recombinant LAL to LAL deficient cells reverses these steps, thus boosting α-HDL formation [18].

There are currently no preventive strategies.

Wolman disease (WD) is often seen in childhood with an estimated incidence of less than 1/300,000 live births and the average survival being about six months [1]. It is caused by mutations in the lysosomal acid lipase gene, thereby producing a defective lysosomal acid lipase (LAL) enzyme. This enzyme is responsible for hydrolyzing cholesteryl esters (CE) and triglycerides (TG) which enter the lysosomes through receptor-mediated endocytosis [2]. The consequence of this deficiency is a massive buildup of CEs and TGs in the macrophages of several organs in the body. Such accumulations in the liver can cause liver cirrhosis, while a buildup in the lungs can lead to pulmonary fibrosis. WD may also result in calcifications in the zona reticularis of the adrenal gland, thus causing adrenal insufficiency [3] [4] [5] [6]. In the intestines, the buildup of TGs and CEs leads to abnormal intestinal absorption leading to massive weight loss. In addition to the above, some patients can develop atherosclerosis due to dyslipidemia [3] [4] [7]. A less severe manifestation of lysosomal acid lipase deficiency is called cholesteryl ester storage disease (CESD).

Bone marrow and umbilical cord blood transplants are promising treatment interventions. However, the lack of matched donors and the severe, fast wasting seen in affected individuals limit the therapeutic efficacy of bone marrow transplantation [5] [6].

Wolman disease is an uncommon disease caused by an abnormal change in the gene that produces an enzyme called lysosomal acid lipase. This leads to a deficiency of this enzyme causing a buildup of fats in body tissues and organs. These dangerous accumulations can occur in the liver, spleen, intestines, lymph nodes and adrenal glands, causing multiple complications in these organs. Wolman disease is an inherited disease wherein affected individuals get a defective gene from each of their parents.

Causes

Wolman disease is caused by an abnormal change in the lysosomal acid lipase gene (LIPA) and two of these abnormal genes are inherited by a patient from each parent. This gene is responsible for the production of lysosomal acid lipase enzyme, which acts inside cells to break down fats. An abnormal LIPA gene leads to the manufacture of a defective enzyme which cannot break down these fats in the cells; hence, these fats accumulate in harmful concentrations inside the cells, thereby causing complications.

Symptoms and clinical features

The symptoms of Wolman disease can vary and most children do not survive beyond 12 months of birth. There might be no symptoms immediately after birth. Between 4 to 8 weeks of age, clinical manifestations begin to appear and progress in a rapid fashion.

The clinical features of this disease include poor feeding with persistent vomiting, distension of the stomach, liver and spleen enlargement, passage of frequent watery or fatty stools, severe wasting or weight loss, enlargement and calcium deposition in the adrenal glands.

Diagnosis

Diagnosis of this disease can be difficult because it is an uncommon condition. The doctor will consider the patient's past medical records, family history, presenting signs and symptoms as well as laboratory and radiological investigations to make a diagnosis of Wolman disease.

Treatment

Research is still ongoing on a definitive treatment for Wolman disease. For now, all that is available is supportive and symptomatic care. Promising treatment options include bone marrow and cord blood transplantation. Similarly, enzyme replacement therapy with synthetic copies of the deficient lysosomal acid lipase enzyme is also under clinical trials and is showing promising results.

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