combined saposin deficiency

Combined Saposin Deficiency: A Rare Lysosomal Storage Disorder

Combined saposin deficiency (CSD) is a rare and fatal infantile storage disorder characterized by severe neurological disease and hepatosplenomegaly. It is caused by a mutation in the gene PSAP, which encodes for a protein called prosaposin.

Key Features:

• Fatal Infantile Disorder: CSD is a life-threatening condition that affects infants.
• Severe Neurological Disease: The disorder is characterized by severe neurological problems, including developmental delays and regression.
• Hepatosplenomegaly: Abnormal enlargement of the liver and spleen (hepatosplenomegaly) is a common feature of CSD.
• Rare Lysosomal Storage Disorder: CSD is an exceedingly rare lysosomal storage disorder, with less than 10 cases reported worldwide.

Causes:

• Mutation in PSAP Gene: The disorder is caused by a mutation in the gene PSAP, which encodes for prosaposin.
• Absence of Saposins: The mutation leads to the absence of all saposins (A, B, C, and D), which are essential cofactors for enzymes involved in lysosomal catabolism.

References:

• [1] Hulkova et al. (2001) - A case study of a male infant with combined saposin deficiency.
• [2-5] Various OMIM reports (#611721) - Detailed information on the disorder, including its causes and clinical features.
• [6-7] Additional reports on CSD, including its fatal infantile nature and severe neurological disease.

Note: The above description is based on the search results provided in the context.

Combined saposin deficiency (PSAPD) is a rare genetic disorder that affects the body's ability to break down certain lipids, leading to their accumulation in various organs and tissues.

Neurological Signs and Symptoms:

• Hypotonia (low muscle tone)
• Massive myoclonic bursts
• Abnormal ocular movements and dystonia
• Grand mal seizures and other types of seizures [3][7]
• Severe neurological manifestations, including early onset with severe symptoms [1]

Hepatosplenomegaly:

• Enlargement of the liver (hepatomegaly)
• Enlargement of the spleen (splenomegaly)

Other Signs and Symptoms:

• Abnormal glycosphingolipid metabolism
• Feeding difficulties
• Abnormality of the eye [5]

Clinical Features:

• Early onset with severe neurological manifestations, hepatosplenomegaly, and early death [1][6]
• Fatal infantile storage disorder characterized by hepatosplenomegaly and severe neurologic disease [8]

Combined saposin deficiency is a rare and serious condition that requires prompt medical attention. If you suspect that someone may be affected by this condition, it's essential to consult with a qualified healthcare professional for proper diagnosis and treatment.

References: [1] Context result 1 [3] Context result 3 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8

Combined saposin deficiency (PSAPD) can be diagnosed through various genetic testing methods.

• Full gene sequencing: This test involves analyzing the entire PSAP gene to identify any mutations that may be causing the condition. [11]
• Deletion/duplication analysis: This test is used to detect deletions or duplications of one or more exons in the PSAP gene. [12]
• PCR with allele-specific hybridization: This test is a molecular genetic test that can identify mutations in the PSAP gene, including deletions and duplications. [12]

The final diagnosis of combined saposin deficiency (PSAPD) is established by identifying the PSAP mutation(s). Additionally, studying sphingolipids in urine sediment can also help confirm the diagnosis, as it shows a massive combined deficiency of sphingomyelinase and other enzymes. [5]

It's worth noting that diagnostic testing for this condition can inform prognosis and clinical management. However, the study of sphingolipidoses, including combined saposin deficiency, is an active area of research, and new diagnostic methods may become available in the future.

References: [11] Combined SAP deficiency: Full gene sequencing. [12] Clinical Molecular Genetics test for Combined saposin deficiency and using Deletion/duplication analysis, PCR with allele specific hybridization offered by Centogene AG - the Rare Disease Company.

Current Status of Drug Treatment for Combined Saposin Deficiency

Combined saposin deficiency (CSD) is a rare and severe genetic disorder characterized by the absence or reduced activity of all four saposins, leading to accumulation of sphingolipids in various tissues. While there is no specific treatment available for CSD, researchers have been exploring potential therapeutic strategies.

Pharmacological Rescue Strategies

Recent studies have investigated the use of monomethylfumarate (MMF), a multiple sclerosis drug, as a potential pharmacological rescue strategy for CSD. The results suggest that MMF may be effective in reducing sphingolipid accumulation and improving symptoms in zebrafish models of CSD [1][2]. However, further research is needed to confirm the efficacy and safety of MMF in humans.

Genetic Rescue Strategies

Another approach being explored is genetic rescue strategies, which involve introducing a functional copy of the PSAP gene into cells to restore saposin production. This method has shown promise in zebrafish models of CSD [1][2]. However, more research is needed to determine its feasibility and effectiveness in humans.

Current Limitations

While these studies offer hope for potential treatments, it's essential to note that there are currently no approved drugs or therapies available for the treatment of combined saposin deficiency. The mode of inheritance is autosomal recessive, and no specific treatment is available [3].

Future Directions

Further research is needed to develop effective treatments for CSD. This may involve exploring new pharmacological agents, improving genetic rescue strategies, or developing novel therapeutic approaches.

References:

[1] by T Zhang · 2023 · Cited by 7 — We examined pharmacological and genetic rescue strategies via water tank administration of the multiple sclerosis drug monomethylfumarate (MMF), and crossing ...

[2] by T Zhang · 2023 · Cited by 7 — A zebrafish model of combined saposin deficiency identifies acid sphingomyelinase as a potential therapeutic target

[3] The mode of inheritance is autosomal recessive. No specific treatment is available. Encephalopathy due to prosaposin deficiency is a very severe metabolic ...

Combined saposin deficiency is a rare lysosomal storage disorder that can be challenging to diagnose due to its similarity with other conditions. Here are some differential diagnoses to consider:

• Krabbe disease: This is a genetic disorder caused by a deficiency of the enzyme galactocerebrosidase (GALC). It leads to the accumulation of galactosylceramide in the brain, resulting in severe neurological symptoms. [1][2]
• Metachromatic leukodystrophy: This is another lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ASA). It leads to the accumulation of sulfatides in the nervous system, resulting in progressive neurological deterioration. [3][4]
• Gaucher disease: This is a genetic disorder caused by a deficiency of the enzyme glucocerebrosidase (GCase). It leads to the accumulation of glucosylceramide in various organs, including the spleen, liver, and bone marrow. [5][6]
• Farber disease: This is a rare lysosomal storage disorder caused by a deficiency of the enzyme acid ceramidase. It leads to the accumulation of ceramides in the nervous system, resulting in severe neurological symptoms. [7][8]

These conditions can present with similar clinical features to combined saposin deficiency, such as progressive neurological deterioration, muscle weakness, and seizures. However, each condition has distinct biochemical and molecular characteristics that can aid in diagnosis.

In particular, Gaucher disease is often associated with the presence of Gaucher cells, which are characteristic foam cells containing glucosylceramide. [9] Chitotriosidase levels may also be elevated in saposin C deficiency. [10]

A comprehensive diagnostic workup, including enzyme assays, genetic testing, and imaging studies, is essential to accurately diagnose combined saposin deficiency and differentiate it from other lysosomal storage disorders.

References:

[1] Combined saposin deficiency (PSAPD) - OMIM #611721

[2] Krabbe disease - OMIM #245300

[3] Metachromatic leukodystrophy - OMIM #250100

[4] Arylsulfatase A deficiency - OMIM #253200

[5] Gaucher disease - OMIM #230800

[6] Glucocerebrosidase deficiency - OMIM #606463

[7] Farber disease - OMIM #228000

[8] Acid ceramidase deficiency - OMIM #601842

[9] Gaucher cells - a characteristic feature of Gaucher disease

[10] Chitotriosidase levels in saposin C deficiency