Combined Saposin Defiency is a very rare

metabolic Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...

and

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...

that is caused by the mutation in a gene PSAP. This disease belongs to

Lysosomal Storage Diseases Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

(LSDs). Because of complete saposin deficiency, it can cause clinical features of 4 diseases( Gaucher’s Disease,

Metachromatic Leukodystrophy Metachromatic leukodystrophy (MLD) is a lysosomal storage disease which is commonly listed in the family of leukodystrophies as well as among the sphingolipidoses as it affects the metabolism of sphingolipids. Leukodystrophies affect the gro ...

, Farber’s Disease, Krabbe’s Disease) to be apparent.

Cause

PSAPD is caused by mutations in a PSAP gene, which is located on the long arm of

chromosome 10 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 134 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tota ...

(10q22.1). PSAPD is inherited in a Autosomal Recessive fashion. Protein PSAP PDB 1m12

Symptoms

Symptoms usually start in infancy or in neonatal age. The signs of this disease are

respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a r ...

hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and his ...

poor feeding Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or liq ...

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus ( myo- "muscle", clonus "spasm") describes a medical sign and, ...

, hyperkinetic movements, clonic seizures,

leukodystrophy Leukodystrophies are a group of, usually, inherited disorders, characterized by degeneration of the white matter in the brain. The word ''leukodystrophy'' comes from the Greek roots ''leuko'', "white", ''dys'', "abnormal" and ''troph'', "growth". ...

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

, abnormality of eye movement and a

neuronal loss A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...

Optic atrophy Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain. Damage and death of these nerve cells, or neurons, leads to characteristic featu ...

was only reported in 1 patient

Pathophysiology

It’s known that Prosaposin is a precursor of a Saposin A,B,C,D. Saposin A is needed to activate galactocerbroside hydrolysis, Saposin B for sulphatide hydrolysis activation, Saposin C for

glucocerebroside Glucocerebroside (also called glucosylceramide) is any of the cerebrosides in which the monosaccharide head group is glucose. Research conducted on glucocerebrosides has shown that glucocerebrosides help support cellular functions in humans, ...

hydrolysis, Saposin D might activate hydrolysis of

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...

. According to one study, Prosaposin might be involved in neuron and glial protection by extracellular secretion and activation of some

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

s. In conclusion, PSAPD might not only cause accumulation of some sphingolipids, but also it can cause neuronal survival crisis (by mechanism mentioned above).

Prevalence

Prevalence is unknown but 10 cases of this diseases had been reported.

Diagnosis

The study of sphingolipids in urine sediment (It shows combined massive elevation of globotriaosylceramide (Gb3), sulphatide and some other sphingolipids) might be useful for a correct orientation towards diagnosis, also bone marrow/liver’s biopsies usually show Gaucher-like macrophages. For the final diagnosis PSAP gene would be tested for

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

Prognosis

Unfortunately, prognosis is poor for this disease.

History

It was first reported by Harzer et al. in 1989

References

External links

{{Lipid storage disorders Rare diseases Genetic diseases and disorders