Cerebral lipidosis, now replaced by the term cerebral sphingolipidoses (lysosomal lipid storage diseases or just sphingolipidoses are also used), is a group of metabolic disorders that arise from genetic mutations (predominantly autosomal recessive), which promote accumulation of lipids (sphingomyelins) and other associated products in the brain and the central nervous system (CNS) [1] [2] [3] [4]. One of the most important features of these conditions is a severe neonatal or infantile form of the disease, distinguished by marked neurological deterioration, convulsions, both upper and lower motor neuron deficits, and weakness, all frequently leading to death in the first few years of life [1] [4] [5] [6] [7]. On the other hand, juvenile and adult forms show a generally slower clinical course with less severe symptoms of neurodegeneration [1] [5] [6] [7]. The following conditions are included in this group [1] [3] [4] [8]:

• GM1 gangliosidosis - Stems from autosomal recessive mutations in the GM1-β-galactosidase gene resulting in the deficiency of the GM1-β-galactosidase enzyme [1].
• GM2 Gangliosidosis - Hexosaminidase A (HEX A) deficiency leads to Tay-Sachs disease (or GM2 gangliosidosis, due to the buildup of GM2 ganglioside) that has a similar clinical presentation to other cerebral lipidoses.
• Sandhoff disease - Mutations in the hexosaminidase B (HEXB) gene lead to a very early onset of psychomotor retardation (many patients present before 9 months of age) and death [9].
• Metachromatic leukodystrophy (MLD) - Deficiency of the arylsulphatase A (ASA) gene is the main pathological event in MLD, which causes a demyelinating form of cerebral lipidosis [1].
• Krabbe disease - Similarly to MLD, Krabbe disease causes a severe and often fatal demyelinating disease in infancy, whereas a much longer life expectancy is seen with juvenile and adult forms [1] [5].
• Gaucher disease - Described as the most common sphingolipidosis (diagnosed in approximately 1 per 50,000-200,000 births), Gaucher disease predominantly presents as a milder form (type I), but a severe neonatal course (type II) and a juvenile onset of intermediate complaints (type III) are described as well [1]. In addition to central nervous system (CNS) complaints, hepatosplenomegaly and anemia/thrombocytopenia are typically encountered [1].
• Niemann-Pick disease - Three types of Niemann-Pick disease exist in the literature - types A and B arise from mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene that result in the accumulation of sphingomyelin in cells [1]. Type A is universally fatal in infancy, whereas type B can present with a highly variable spectrum of symptoms, but a normal life expectancy can be observed without prominent CNS symptoms [1]. Conversely, Niemann-pick disease type C (NPC) is a lysosomal storage disease caused by defects in cholesterol transport, but it also results in sphingomyelin accumulation, with vertical gaze palsy being a clinical hallmark in addition to CNS symptoms [1] [6].

• Short Stature

  stature and eye abnormalities Type C Symptoms of the type C form of Niemann-Pick disease usually begin to appear in children around 5 years old. [healthline.com]

• Veterinarian

  Designed for the mixed practice large animal veterinarian, veterinary students, and camelid caretakers alike, Llama and Alpaca Care covers all major body systems, herd health, physical examination, nutrition, reproduction, surgery, anesthesia, and multisystem [books.google.de]

• Congestive Heart Failure

  Disease Cirrhosis of the Liver Coarctation of the Aorta Colostomy Congestive Heart Failure Cooley's Anemia Cor Pulmonale Coronary Artery Disease (C.A.D.) [vaughns-1-pagers.com]

• Hypertension

  Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers have been used to treat proteinuria and hypertension. [emedicine.medscape.com]

• Muscle Weakness

  Early symptoms often include clumsiness, problems balancing, and muscle weakness in the legs. People with it may also have mental health issues. With this form of the disease, life expectancy and the severity of symptoms vary from case to case. [webmd.com]

  Muscle weakness or lack of muscle control is common in people with MLD and is a result of this type of damage to the nerves. MLD is a rare disorder that’s reported to occur in one in 40,000 to 160,000 people worldwide. [healthline.com]

• Seizure

  In the gangliosidoses and late in the course of the leukodystrophies, seizures will present management problems... [ncbi.nlm.nih.gov]

  These specialists can help you manage your baby ’s seizures with medication. Respiratory health. [webmd.com]

  With types C and D NPD, there is significant nervous system damage leading to severe muscle spasms, seizures, and eventually coma and death. [encyclopedia.com]

• Ataxia

  Neurological examination revealed uncontrolled movements of mouth and tongue, hypotonia, ataxia of upper and lower extremities, and alternate move- ments were carried out in an inco-ordinate fashion. No visual disturbances were present. [docslide.com.br]

  Página 80 - An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia ataxia and areflexia). N. Engl. J. Med. 255, 57-65. [books.google.es]

  Onset in childhood with dementia; evolving in adolescence with progressive ataxia, spasticity, and cataracts; and finally in adulthood with xanthomas of the tendons, lungs, and brain in the presence of normal or nearly normal blood cholesterol and high [whonamedit.com]

• Behavior Problem

  Preventing serious behavior problems through skill development and early intervention. In AC Repp & NN Singh (Eds.), Perspectives on the use of nonaversive and aversive interventions for persons with developmental disabilities (pp. 273-286). [books.google.com]

  problems decreased mental function decreased muscle tone difficulty walking difficulty eating or feeding frequent falls incontinence irritability a loss of muscle control problems with nerve function seizures difficulty speaking difficulty swallowing [healthline.com]

  Often with J-MLD, the first signs include behavioral problems or new difficulty in school. All forms of MLD are progressive. In late-infantile MLD, within months of the first symptoms, most children lose the ability to talk and walk. [rarediseases.org]

• Opisthotonus

  Two days after admission, opisthotonus accompanied with loss of con- sciousness was noted. Afterwards she be- came bedridden but was discharged from the Clinic without amelioration in her con- dition. She was re-admitted in April 1966. [docslide.net]

• Neurologic Manifestation

  A case study of combined ERT and SRT revealed improvement of neurological signs in symptomatic patients with Gaucher disease type 3 and, over a 3-year observation period, demonstrated prevention of further neurological manifestations in a young child [emedicine.medscape.com]

The diagnosis of cerebral lipidoses must be suspected when a neonatal or infantile onset of progressive neurological and psychomotor decline is observed. But in order to confirm clinical suspicion, a detailed patient history and a comprehensive physical examination are mandatory steps. Given the autosomal recessive pattern of inheritance, a positive family history may provide useful information. As soon as a presumptive diagnosis is made, directed genetic and biochemical studies should be employed. Several laboratory techniques have been described, but a rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) assay provides a quantitative method used to evaluate lysosphingolipids in blood. This is a superior procedure that provides enough information to confirm lipid accumulation [4] [5] [6] [7] [8]. Molecular genetic testing (DNA sequencing) that allows identification of specific gene mutations can be performed to verify the diagnosis [5] [6] [7] [9].

Treatment Treatment focuses on prevention of symptoms and long-term complications. [encyclopedia.com]

Eliglustat was approved in August 2014 as first-line treatment for the long-term treatment of adults with Gaucher disease type 1. [emedicine.medscape.com]

GvHD may cause: a fever a rash diarrhea liver damage lung damage The treatment for MLD includes drugs that suppress the immune system. The treatment will stop the attack but make you more likely to get an infection. [healthline.com]

Prognosis Children born with Tay-Sachs disease become increasingly debilitated; most die by about age four. [encyclopedia.com]

Important information is provided, which, though rarely of therapeutic value, does increase precision of diagnosis, prognosis, and genetic advice (Cumings, 1965a, b, c; Poser, 1962; Adams, 1965). [semanticscholar.org]

Prognosis It is important to know that many children with ASD have bright futures and can achieve their goals. [cinaps.co.uk]

PMID: 24119781 Prognosis Cariati I, Masuelli L, Bei R, Tancredi V, Frank C, D'Arcangelo G Int J Mol Sci 2021 Jun 20;22(12) doi: 10.3390/ijms22126600. PMID: 34202978Free PMC Article Lyssenko NN, Praticò D Alzheimers Dement 2021 Feb;17(2):164-174. [ncbi.nlm.nih.gov]

Etiology J Neurol 2021 Oct;268(10):3878-3885. Epub 2021 Apr 8 doi: 10.1007/s00415-021-10535-4. [ncbi.nlm.nih.gov]

Some Epidemiologic and Genetic Aspects of Tay-Sachs' Disease 27. Genetic and Demographic Considerations Concerning Tay-Sachs' Disease 28. Genetics of the Sphingolipidoses 29. [elsevier.com]

Friedman, CR, Neimann, J., Wegener, HC, and Tauxe, RV Epidemiology of Campylobacter jejuni infections in the United States and other industrialized nations. [books.google.es]

Descriptive epidemiology of Fabry disease among beneficiaries of the Specified Disease Treatment Research Program in Japan. J Epidemiol. 2012. 22(4):370-4. [Medline]. Goldim MP, Garcia Cda S, de Castilhos CD, Daitx VV, Mezzalira J, Breier AC, et al. [emedicine.medscape.com]

Pathophysiology of Gestation deals with the underlying mechanisms of disorders affecting fetuses and neonates, especially those that happen during the early neonatal period. [books.google.es]

Health science Providing basic knowledge of medical terminology, anatomy and physiology, and pathophysiology of diseases and conditions. [icd-10online.com]

Though this procedure will not reverse damage already done by the disease, it can stop future damage to the nervous system and prevent mental disability for some people. [healthline.com]

Preventing serious behavior problems through skill development and early intervention. In AC Repp & NN Singh (Eds.), Perspectives on the use of nonaversive and aversive interventions for persons with developmental disabilities (pp. 273-286). [books.google.com]

Can It Be Prevented? You can have a blood test that analyzes your genes or the levels of the Hex-A protein in your blood to tell you whether you are a carrier. [webmd.com]

Treatment Treatment focuses on prevention of symptoms and long-term complications. [encyclopedia.com]

1. Schulze H, Sandhoff K. Lysosomal Lipid Storage Diseases. Cold Spring Harb Perspect Biol. 2011;3(6):a004804.
2. Rieger D, Auerbach S, Robinson P, Gropman A. Neuroimaging of lipid storage disorders. Dev Disabil Res Rev. 2013;17(3):269-282.
3. Ozkara HA, Topçu M. Sphingolipidoses in Turkey. Brain Dev. 2004 Sep;26(6):363-366.
4. Platt FM, Boland B, van der Spoel AC. Lysosomal storage disorders: The cellular impact of lysosomal dysfunction. J Cell Biol. 2012;199(5):723-734.
5. Pavuluri P, Vadakedath S, Gundu R, Uppulety S, Kandi V. Krabbe Disease: Report of a Rare Lipid Storage and Neurodegenerative Disorder. Muacevic A, Adler JR, eds. Cureus. 2017;9(1):e949.
6. Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis. 2010;5:16.
7. Kaback MM, Desnick RJ. Hexosaminidase A Deficiency. 1999 Mar 11 [Updated 2011 Aug 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
8. Polo G, Burlina AP, Kolamunnage TB, Zampieri M, Dionisi-Vici C, Strisciuglio P, Zaninotto M, Plebani M, Burlina AB Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS. Clin Chem Lab Med. 2017;55(3):403-414.
9. Delnooz CC, Lefeber DJ, Langemeijer SM, et al. New cases of adult-onset Sandhoff disease with a cerebellar or lower motor neuron phenotype. J Neurol Neurosurg Psychiatry. 2010;81(9):968-972.