Wolman Disease (LIPA p.G87V) Genotype Frequency in People of Iranian-Jewish Ancestry

Valles-Ayoub, Yadira; Esfandiarifard, Saghi; No, Daniel J.; Sinai, Pedram; Khokher, Zeshan; Kohan, Melody; Kahen, Tanaz; Darvish, Daniel

doi:10.1089/gtmb.2010.0203

Cited by 37 publications

(29 citation statements)

References 7 publications

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“…WD occurs more frequently in Iranian-Jewish populations (1 in 4,200 newborns) and in areas of the Galilee [14]. Wolman himself pointed out that even in areas with higher than average rates of WD, clinical awareness for WD may not be high, leading to underreporting [12].…”

Section: Introductionmentioning

confidence: 99%

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

Aguisanda

Thorne

Zheng

2017

Curr. Chem. Genomics and Translat. Med.

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Wolman disease (WD) and cholesteryl ester storage disease (CESD) are lysosomal storage diseases (LSDs) caused by a deficiency in lysosomal acid lipase (LAL) due to mutations in the LIPA gene. This enzyme is critical to the proper degradation of cholesterol in the lysosome. LAL function is completely lost in WD while some residual activity remains in CESD. Both are rare diseases with an incidence rate of less than 1/100,000 births for WD and approximate 2.5/100,000 births for CESD. Clinical manifestation of WD includes hepatosplenomegaly, calcified adrenal glands, severe malabsorption and a failure to thrive. As in CESD, histological analysis of WD tissues reveals the accumulation of triglycerides (TGs) and esterified cholesterol (EC) in cellular lysosomes. However, the clinical presentation of CESD is less severe and more variable than WD. This review is to provide an overview of the disease pathophysiology and the current state of therapeutic development for both of WD and CESD. The review will also discuss the application of patient derived iPSCs for further drug discovery.

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Section: Introductionmentioning

confidence: 99%

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

Aguisanda

Thorne

Zheng

2017

Curr. Chem. Genomics and Translat. Med.

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“…It is thought to occur in approximately 1 in 350,000 newborns worldwide and has an autosomal‐recessive inheritance pattern. In the Iranian‐Jewish population, as many as 1 in 4,200 newborns may be affected . The inability to catalyze the hydrolysis of cholesterol esters and triglycerides results in massive accumulation of lysosomal esterified lipids throughout the body, including the liver, spleen, bone marrow, and gut .…”

Section: Introductionmentioning

confidence: 99%

Prenatal sonographic findings in a case of Wolman's disease

Blitz

Rochelson

Sood

et al. 2017

J of Clinical Ultrasound

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No published case of Wolman's disease has described the prenatal sonographic findings. We present a case in which a third-trimester sonographic examination demonstrated fetal hepatomegaly and bilateral adrenal echogenicity suggestive of diffuse calcification. Wolman's disease, also known as lysosomal acid lipase (LIPA) deficiency, is a rare autosomalrecessive disorder characterized by complete absence of the LIPA enzyme. The diagnosis of Wolman's disease was made postnatally by biochemical testing, which indicated absence of LIPA enzyme activity and gene sequencing, which confirmed homozygosity for the G66V mutation within the LIPA gene. V C 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:66-68, 2018; Published online in Wiley Online Library (wileyonlinelibrary.com).

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“…The exact prevalence of LAL‐D in children and adults is not yet established, and ranges from 1 in 150,000 to 1 in 350,000 in Caucasian populations . However, LAL‐D seems to occur at a higher frequency in the Iranian‐Jewish community residing in the Los Angeles area, with an overall carrier frequency for the p.Gly87Val mutation of 1:32.4 (3.086%), deducing a much greater prevalence in this population (1 in 4200) . Population screening for the c.894G>A mutation among healthy West German individuals indicated a heterozygote frequency of 1 in 200 individuals .…”

Section: Discussionmentioning

confidence: 99%

Opening a window on lysosomal acid lipase deficiency: Biochemical, molecular, and epidemiological insights

Cappuccio

Donti

Hubert

et al. 2019

J of Inher Metab Disea

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Lysosomal acid lipase deficiency (LAL-D) is a multi-organ autosomal recessive disease caused by mutations in LIPA. We reviewed data from 681 samples (white blood cells [WBC] n = 625, fibroblasts = 30, liver = 4, amniocytes = 13, chorionic villus = 9) received for analysis of lysosomal acid lipase (LAL) activity over a 15-year period. LIPA sequencing was performed in 49 patients with reduced (n = 26) or deficient (n = 23) LAL activity. The Exome Aggregation Consortium and Genome Aggregation Database dataset were used for LAL-D prevalence calculations. LAL WBC activity was reduced in 67 patients (10.72%) and deficient in 37 (5.92%). The average of LAL activity ± margin of error (CI 95%) was 19.32 ± 0.86 pmol/min/mg for reduced activity patients and 5.90 ± 1.42 pmol/min/mg for deficient patients. The average age at diagnosis for LAL-D was 23.6 years with several patients older than age 30. The correlation between the age at diagnosis and LAL activity showed a significant moderate direct correlation (Pearson's r = 0.46, P < 0.005). Homozygous or compound heterozygous mutations were identified in 9 out of 23 patients with deficient results (detection rate 39.1%). The average LAL activity in molecularly confirmed patients was 4.02 ± 2.02 pmol/min/mg protein, while in molecularly negative patients was 13.886 ± 1.49 pmol/min/mg (P < 0.0001). Twenty-two different mutations were identified including two novel variants (c.309C>A and c.856G>C). A carrier frequency of approximately 1 in 350 was inferred. LAL activity in WBC is a validated tool for LAL-D diagnosis. Higher residual enzymatic activity might result in a milder phenotype leading to diagnosis delay. A cut-off below 12 pmol/min/mg protein might be useful to discriminate patients with LIPA mutations.

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Wolman Disease (LIPA p.G87V) Genotype Frequency in People of Iranian-Jewish Ancestry

Cited by 37 publications

References 7 publications

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

Prenatal sonographic findings in a case of Wolman's disease

Opening a window on lysosomal acid lipase deficiency: Biochemical, molecular, and epidemiological insights

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