Rare Pulmonology News

Disease Profile

Sphingosine phosphate lyase insufficiency syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Primary adrenal insufficiency-steroid-resistant nephrotic syndrome due to SGPL1 deficiency; SPL insufficiency syndrome; SPLIS;

Summary

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is a very rare condition that affects the kidneys, adrenal glands and nervous system. Symptoms vary from individual to individual, but most people with SPLIS have signs of abnormal kidney and adrenal gland function, which can include a buildup of extra fluid, vomiting and diarrhea. Some people with SPLIS have dry, scaly, cracked or darkened skin and problems with their immune system. Some people with SPLIS have neurological problems that can include nerve-related hearing loss, a drooping eyelid, tingling in arms and legs, difficulty moving limbs, or seizures [1][2]. SPLIS is caused by genetic changes (mutations) of the sphingosine-1-phosphate lyase 1 gene (SGPL1) and is inherited in an autosomal recessive pattern [3]. SPLIS is diagnosed based on the symptoms, clinical examination, and through genetic testing. There is no specific treatment for SPLIS [4]. Medication and supportive care can help with some of the symptoms. The long-term outlook for people with these disorders is unknown.

Symptoms

Although the age of onset is not the same for everyone, the signs and symptoms of sphingosine phosphate lyase insufficiency syndrome (SPLIS) usually appear in infancy or early childhood. Some people with SPLIS may be more severely affected than others, with the most severe form of this condition resulting in early fetal death due to excess fluid accumulation. Some of the more common signs and symptoms of SPLIS include: 

Steroid-resistant nephrotic syndrome (SRNS) 
Build-up of fluid (edema)
Loss of protein in the urine
Adrenal insufficiency
Weight loss
Fatigue
Dark, patchy skin
Vomiting, diarrhea and severe dehydration
Ichthyosis (dry, thickened, scaly skin)
Neurological problems: muscle weakness, muscle wasting, problems with movement, and developmental delay

Other organs that may be affected include the eyes, the heart and the gonads (sex organs).[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Adrenal insufficiency
0000846
Ataxia
0001251
Autosomal recessive inheritance
0000007
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Diffuse mesangial sclerosis
0001967
Edema
Fluid retention
Water retention

[ more ]

0000969
Focal segmental glomerulosclerosis
0000097
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Hypoalbuminemia
Low blood albumin
0003073
Hypoglycemia
Low blood sugar
0001943
Hypogonadism
Decreased activity of gonads
0000135
Hypothyroidism
Underactive thyroid
0000821
Ichthyosis
0008064
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number

[ more ]

0001888
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Micropenis
Short penis
Small penis

[ more ]

0000054
Nephrotic syndrome
0000100
Peripheral neuropathy
0009830
Progressive
Worsens with time
0003676
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
Ptosis
Drooping upper eyelid
0000508
Seizure
0001250
Sensorineural hearing impairment
0000407
Stage 5 chronic kidney disease
0003774
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Variable expressivity
0003828

Cause

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is caused by mutations in the spingosine-1-phosphate lyase 1 (SGPL1) gene. The protein made by this gene is found in many different organs, including the thymus, intestines, lymph nodes, brain, kidneys, adrenal gland and other endocrine glands. It is involved in many important processes of cellular function.[4]

Diagnosis

Sphingosine phosphate lyase insufficiency (SPLIS) is diagnosed based on symptoms, clinical examination and by genetic testing.[4]

Treatment

The treatment for people with sphingosine phosphate lyase insufficiency syndrome (SPLIS) is focused on treating specific symptoms, such as dialysis or kidney transplantation for kidney failure and hormone replacement for adrenal gland failure.[4]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

References

  1. Linhares ND, Arantes RR, Araujo SA, Pena SDJ. Nephrotic syndrome and adrenal insufficiency caused by variant in SGPL1. Clin Kidney Jl. Aug 2018; 11(4):462-467. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070023/.
  2. Janecke AR, Xu R, Steichen-Gersdorf E, Waldegger S, Entenmann A, Giner T, et al. Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with congenital nephrotic syndrome and congenital adrenal calcifications. Hum Mutat. Apr 2017; 38(4):365-372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384969.
  3. Lovric S, Goncalves S, Gee HY, Oskouian B, Srinivas H, Choi WI, et al. Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. J Clin Invest. Mar 1 2017; 127(3):912-928. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330730/.
  4. Choi YJ, Saba JD. Sphingosine phosphate lyase insufficiency syndrome (SPLIS): A novel inborn error of sphingolipid metabolism. Adv Biol Regul. Jan 2019; 71:128-140. https://www.ncbi.nlm.nih.gov/pubmed/30274713.

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