Ceramides in a Patient with Lipogranulomatosis (Farber's Disease) with Chronic Course

Samuelsson, Karin; Zetterström, Rolf

doi:10.3109/00365517109080235

Cited by 41 publications

(23 citation statements)

References 20 publications

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“…A mild type has been described in two sisters and their female cousin [17] and in two additional patients [2,18]. These patients survive longer; two died at the age of 16 and 17 years, respectively, while the others were still alive at the ages of 9, 13 and 17 years, respectively.…”

Section: Discussionmentioning

confidence: 94%

A case of lipogranulomatosis Farber: some clinical and ultrastructural aspects

Burck¹,

Moser

Goebel

et al. 1985

Eur J Pediatr

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A 20-month-old girl showed typical clinical signs of Farber disease: hoarseness since birth, and periarticular subcutaneous painful nodules. Complete deficiency of acid ceramidase activity was found in cultured skin fibroblasts. An electron microscopic examination of a dermal nodule disclosed pathognomonic tubular inclusions in histiocytes. In epidermal cells zebra-body-like and needle-like lysosomal inclusions were found. Their ultrastructure is different from that of the intrahistiocytic lysosomal inclusions. Probably three clinical types of Farber disease may be distinguished according to the symptomatology and the course of the disease: a severe type, an intermediate type and a relatively mild type. The activity of acid ceramidase does not correlate with prognosis of the disease, while a correlation between first appearance of dermal nodules and clinical course appears likely.

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Section: Discussionmentioning

confidence: 94%

A case of lipogranulomatosis Farber: some clinical and ultrastructural aspects

Burck¹,

Moser

Goebel

et al. 1985

Eur J Pediatr

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“…[35][36][37] Patients with this phenotype may survive into the fourth decade of life and do not have neurological or visceral involvement, but they develop progressive lipogranulomata (often on the eyelids, nares and mouth), hoarseness, laryngeal nodules, joint deformities and contractures. In this situation, transplant-related mortality must be balanced against the progressive disfigurement and loss of joint mobility that occur in this phenotype.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow transplantation for infantile ceramidase deficiency (Farber disease)

Yeager

Uhas

Coles

et al. 2000

Bone Marrow Transplant

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Summary:Infantile ceramidase deficiency (Farber disease) is an uncommon, progressive lysosomal storage disease characterized by multiple ceramide-containing nodules (lipogranulomata) in the subcutaneous tissue and upper aerodigestive tract, painful periarticular swelling, psychomotor retardation, and varying degrees of ocular, pulmonary or hepatic involvement. Management of Farber disease has been limited to symptomatic supportive care, and few affected infants survive beyond 5 years of age. We performed an allogeneic bone marrow transplant (BMT) from an HLA-identical heterozygous sister in a 9.5-month-old female with minimally symptomatic Farber disease who received a pre-transplant regimen of busulfan and cyclophosphamide. Ceramidase activity in peripheral blood leukocytes increased from 6% before transplant to 44% (donor heterozygote level) by 6 weeks after BMT. By 2 months after transplant, the patient's subcutaneous lipogranulomata, pain on joint motion, and hoarseness had resolved. Despite modest gains in cognitive and language development, hypotonia and delayed motor skills persisted. Gradual loss of circulating donor cells with autologous hematopoietic recovery occurred; VNTR analyses showed 50% donor DNA in peripheral blood cells at 8.5 months after BMT and only 1% at 21 months after transplant. Interestingly, leukocyte ceramidase activity consistently remained in the heterozygous range despite attrition of donor cells in peripheral blood. This novel observation indicates ongoing hydrolase production by non-circulating donor cells, possibly in the mononuclear phagocytic system, and uptake by recipient leukocytes. Although lipogranulomata and hoarseness did not recur, the patient's neurological and neurocognitive status progressively declined. She died 28 months after BMT (age 37.5 months) with pulmonary insufficiency caused by recurrent aspiration pneumonias. Allogeneic BMT

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“…Lipid accumulation is mainly seen in the joints, tissues, and the central nervous system, but also in liver, heart, and kidneys. Ceramide accumulation in the kidney leading to a particular phenotype of lipogranlulomatosis was described (52). …”

Section: Sphingolipid Accumulation and Glomerular Disease Of Genetic mentioning

confidence: 99%

Podocyte Pathology and Nephropathy â€“ Sphingolipids in Glomerular Diseases

Merscher

Fornoni

2014

Front. Endocrinol.

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Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay–Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann–Pick, and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarly, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD), HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS), and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine, and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is expressed in podocytes where it modulates acid sphingomyelinase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

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Ceramides in a Patient with Lipogranulomatosis (Farber's Disease) with Chronic Course

Cited by 41 publications

References 20 publications

A case of lipogranulomatosis Farber: some clinical and ultrastructural aspects

A case of lipogranulomatosis Farber: some clinical and ultrastructural aspects

Bone marrow transplantation for infantile ceramidase deficiency (Farber disease)

Podocyte Pathology and Nephropathy â€“ Sphingolipids in Glomerular Diseases

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