LAL deficiency, also known as Wolman disease, is a lethal genetic lipid storage disease that is caused by the lack of lysosomal acid lipase (Lipase A) enzyme. (Lipase A) is important in breaking down (catabolism) low-density lipoproteins (triglycerides and cholesterol esters). Absence of active enzyme leads to accumulation of large amounts of these lipids in cells. Therefore, the normal metabolic functions of the cells are impaired causing severe neurological and physical symptoms which end with early death.
Infants with LAL deficiency are normal and active at birth, but rapidly develop progressive mental deterioration, hepatosplenomegaly, distended abdomen, gastrointestinal problems (steatorrhea), jaundice, anemia, vomiting and calcification of the adrenal glands. In addition, hyperlipidemia type IIb is common in LAL deficiency. The milder form of the disease is cholesterol ester storage disease (CESD). Patients with CESD may not show symptoms until adulthood, whereas severe Wolman disease is usually fatal by age one. Overall, the progression of the disease is related to how much Lipase A enzyme is active. The early onset form of LAL deficiency has a reported incidence of 2 births per million in a general population.
LAL deficiency goes by several different names in the medical literature. This is mainly represents a lack of awareness and experience with the disease more than variance in its molecular causes. In addition, certain genetic conditions may also be mistaken for early onset forms of the disease. These include: Hirschprung's disease, Niemann-Pick C, gastroenteritis, pyloric stenosis, histiocytosis, lymphoproliferative disease, and childhood cirrhosis.
There is no specific treatment for LAL deficiency. However, patients with anemia may require blood transfusions. Moreover, the enlarged spleen must be removed to improve cardiopulmonary function. Lipid free diet does not prevent lipid building up in the cells.
Zein Aldeen et al. (1999) described the first two cases with Wolman's disease in Bahrain. The first case was 3-month-old male infant of consanguineous parents. He had history of diarrhea, vomiting, abdominal distention and failure to thrive. Abdominal X-ray showed two massive punctuate calcific paravertebral shadow. Chest X-ray and skeletal survey showed osteopenia. His condition deteriorated and died few hours after admission. Postmortem microscopic examination revealed the presence of large foamy lipid-laden histiocytes in different parts like; liver, spleen, bone marrow, kidney, and mesenteric lymph nodes. Amorphous partly calcific masses were present throughout the inner cortex of the adrenals. In the aorta, lipid deposition was seen between the elastic fibers. The second case was 2 and half-month-old female infant of healthy second degree consanguineous parents. Her abdomen was distended and the bowel sounds were audible. Bilateral adrenal calcification, hepetosplenomegaly, and thickened intestinal loops were observed in X-ray and ultrasound. Her condition deteriorated rapidly and died of septic shock. In both cases, there was no evidence of familial transmission; therefore Zein Aldeen et al. (1999) suggested that Wolman disease without familial transmission might exist.
[Zein Aldeen HA, Al-Hilli F, Mohammad AM, Jamsheer NS, Romani KHR. Wolman's disease. The first two cases from Bahrain. Bahrain Med Bull. 1999; 21(1):24-6.]
Shome et al. (2002) studied the clinical and morphological features of two Bahraini infants with Wolman disease. One of the patients was a 16-hour-old male. He had abdominal distention few hours after birth. At the age of nine weeks, the frequency of vomiting and diarrhea was increased. He had anemia and abnormal morphological blood features. Mild hypoalbuminemia and numerous stool fat globules were detected. During the next few weeks, there was a progressive wasting with loose skin folds. Radiological examination and ultrasounds revealed distended bowel loops, splenomegaly, hepatomegaly, and no adrenal calcification. Thickened bowel walls were noted. The marrow aspirate showed a prominent increase in macrophages with marked vacuolation. Serum acid lipase isoenzyme A was markedly reduced and peripheral blood leukocytes assay also had reduced acid lipase activity. Hepatocellular failure appeared after six weeks which was identified by gradually rising serum bilirubin and transaminases. Finally, the patient died. The other patient was 11-week old male who was presented to the hospital with a one day history of fever, watery diarrhea, and vomiting. He was noticed to have abdominal distention with umbilical hernia, hepatomegaly, splenomegaly, and severe anemia. Hemoglobin electrophoresis and HPLC revealed 6% hemoglobin Bart's that was associated with alpha thalassemia. The results of the biochemical and hormonal tests were hypoalbuminemia, raised cholesterol, low HDL level, hypertriglyceridemia, and raised cortisol level. X-ray and ultrasound of the abdomen showed bilateral adrenal enlargement and multiple foci of calcification. Foamy macrophages and vacuolated leukocytes were observed in marrow aspirate. The baby passed away six weeks after admission. Shome et al. (2002) suggested that Wolman disease might not be rare in the Bahraini population.
Yousef et al. (2005) reported the first case of Wolman disease in an Egyptian patient. This 15-week old baby girl, first-born to consanguineous parents, presented with a history of failure to thrive and abdominal distension. She was found to be pale with hypotonia and massive hepatosplenomegaly. Blood and bone marrow analysis revealed anemia with thrombocytopenia, and the presence of vacuolated lymphocytes and foamy cells. Abdominal radiograph revealed calcification in the supra-renal regions, large liver and splenic shadows, and dilated bowel loops, with a generalized diminished bone density. Ultrasound showed large hyperechoic adrenal glands with bilateral adrenal calcifications. Abdominal CT scan indicated fatty infiltration, while all the above findings were confirmed by MRI. A diagnosis of Wolman disease was made. The child had progressive hepatic failure and assumed septicemia and died at the age of five-months.
[Yousef TM, Shafik MH, Shalan YAF. Wolman disease in an egyptian patient. Kuwait Med J. 2005; 37(3):200-2.]
Mahdi et al. (1991) reported a case of Wolman's disease for the first time in a Jordanian infant. The clue to diagnosis was the radiological evidence of bilateral adrenal calcifications and foam cells in bone marrow. The disease was confirmed by skin fibroblast culture which showed decreased 'acid esterase' activity.
[See: Egypt > Yousef et al., 2005]
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Lysosomal storage disorders were the most diagnosed category of IEM in this cohort (74 out of 248 cases, 30%). Among them, one case was found to have Wolman disease with an estimated incidence of 1 per 100,000 live births. All cases of lysosomal storage disorders were confirmed enzyme assay on skin fibroblast, liver biopsy or leukocytes. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.
Mnif et al. (1994) reported a boy, born to consanguineous parents, with Wolman Disease. His weight was 3,500 g, height 53 cm. Hepatomegaly was observed at the age of 26 days; he also had vomiting and watery stools with failure to thrive. Diagnosis of Wolman disease was suspected due to family history. Two sisters had died at the age of 3 months without precise diagnosis; both had abdominal distension, hepatosplenomegaly, anemia and inanition; CT scan showed calcifications of adrenal glands in one of them that had been attributed to adrenal hemorrhage. Liver biopsy showed enlarged and vacuolated parenchymal and Kupffer cells but the marrow did not contain foam cells. Acid lipase deficiency was demonstrated in cultured skin fibroblasts, permitting prenatal diagnosis in a further sib.