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disorder of phospholipids, sphingolipids and fatty acids biosynthesis - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

disorder of phospholipids, sphingolipids and fatty acids biosynthesis

MONDO:0018117

Overview

OnsetINFANTILE

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: infancy.

GeneReviews

Clinical Guidance

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is characterized by varying combinations of steroid-resistant nephrotic syndrome, primary adrenal insufficiency (with or without mineralocorticoid deficiency), testicular insufficiency, immunodeficiency, and neurologic abnormalities, and may also include primary hypothyroidism and ichthyosis. To date, 46 individuals with sphingosine phosphate lyase insufficiency syndrome (SPLIS) have been reported [, , , , , , , , , , ]. Of note, the individual reported by is also included in the report by . The following description of the phenotypic features of SPLIS is based on these reports. Table 2. Features of Sphingosine Phosphate Lyase Insufficiency Syndrome

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) should be suspected in individuals with any combination of the following clinical, laboratory, and imaging findings and family history.

Clinical findings

Steroid-resistant nephrotic syndrome. Typically congenital or infantile-onset, often associated with focal segmental glomerulosclerosis

• Endocrine

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for disorder of phospholipids, sphingolipids and fatty acids biosynthesis. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with sphingosine phosphate lyase insufficiency syndrome (SPLIS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with Sphingosine Phosphate Lyase Insufficiency Syndrome

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

There are no published surveillance guidelines. Based on the known potential medical conditions associated with SPLIS, we propose consideration of the following . Table 7. Recommended Surveillance for Individuals with Sphingosine Phosphate Lyase Insufficiency Syndrome

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for disorder of phospholipids, sphingolipids and fatty acids biosynthesis.

73 publications have been identified in PubMed for disorder of phospholipids, sphingolipids and fatty acids biosynthesis. Research spans Basic Science / Preclinical (56%), Review / Meta-Analysis (25%), and Epidemiology / Natural History (10%).

Research Type	Count	% of Total
Laboratory research	41	56%

Data assembled from 4 of 12 sources · Last updated Sep 20, 2026, 5:14 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:352301

GARD

Genetic and Rare Diseases Info Center

GARD:21516

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

Feature	# of Persons	Comment
Steroid-resistant nephrotic syndrome	37/46	—
Endocrine	Primary adrenal insufficiency	31/46
8/26 w/cryptorchidism /or micropenis Hypothyroidism	6/46	—
Immunodeficiency	31/46	—
Neurologic abnormalities	22/46	Cranial nerve deficits (11/46); Strabismus (6/46); Ptosis (2/46); Developmental delay (9/46); Regression/progressive neurologic involvement (6/46); Peripheral motor sensory neuropathy (5/46)
Spasticity Sensorineural hearing loss	8/45	—
Ichthyosis/acanthosis	13/46	1. , , The range of renal involvement extends from nonimmune fetal hydrops at the severe end to delayed evidence of nephrosis for many years after diagnosis or no renal involvement after years of follow up, as observed in two sibs in their twenties and thirties .

GeneReviews

Differential Diagnosis

Table 3. Genes of Interest in the Differential Diagnosis of Sphingosine Phosphate Lyase Insufficiency Syndrome

Gene(s)	DiffDx Disorder(s)	MOI	Features of the DiffDx Disorder
ALDH3A2	Sjgren-Larsson syndrome 1	AR	Ichthyosis; intellectual disability; abnormal brain MRI
GBA1 (GBA)	Gaucher disease type 2	AR	Ichthyosis; nonimmune hydrops; abnormal brain MRI
LAMB2	Pierson syndrome (OMIM 609049)	AR	Steroid-resistant nephrotic syndrome; developmental delay
Lysosomal acid lipase deficiency	AR	Adrenal calcifications	Hepatic fibrosis cirrhosis; intestinal malabsorption LMX1B
Nail-patella syndrome	AD	Steroid-resistant nephrotic syndrome; sensorineural hearing loss	Nail dysplasia; hypoplastic or absent patellae; eye anomalies NPHS1 NPHS2
PLCE1	Congenital nephrotic syndrome types 1, 2, 3 (OMIM 256300, 600995, 610725)	AR	Steroid-resistant nephrotic syndrome
Schimke immunoosseous dysplasia	AR	Steroid-resistant nephrotic syndrome; T-cell lymphopenia	Spondyloepiphyseal dysplasia; numerous lentigines AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; MOI = mode of inheritance; SPLIS = sphingosine phosphate lyase insufficiency syndrome 1. Table 4.
Differential Diagnosis of Clinical Findings Associated with Sphingosine Phosphate Lyase Insufficiency Syndrome Clinical Finding	Distinguishing Features	Comment	—
Motor/sensory neuropathy	Often autosomal dominant	See Charcot-Marie-Tooth Hereditary Neuropathy Overview.	—
Congenital ichthyosis	Acanthosis may be observed in SPLIS.	Congenital ichthyosis is a feature of several genetic syndromes.; Nonsyndromic ichthyosis (e.g., autosomal recessive congenital ichthyosis) can be considered if ichthyosis is the presenting finding; syndromic ichthyosis can be assoc w/Netherton syndrome, Sjgren-Larsson syndrome, trichothiodystrophy	—
Nonimmune hydrops	Enlarged/hemorrhagic adrenals	Many genetic conditions are assoc w/fetal hydrops (e.g., chromosome anomalies, RASopathies, lysosomal storage disorders).1 Primary adrenal insufficiency	Adrenal calcifications, hypothyroidism, cryptorchidism, micropenis may be assoc w/primary adrenal insufficiency.

Source: GeneReviews — "Sphingosine Phosphate Lyase Insufficiency Syndrome"

System/Concern	Evaluation	Comment
syndrome	Referral to nephrologist	Serum creatinine/BUN; urine protein/creatinine; renal ultrasound; May require kidney biopsy Primary adrenal
insufficiency	Endocrinology referral	Early morning ACTH cortisol; Serum electrolytes; Plasma renin activity; Adrenal ultrasound; ACTH stimulation test if baseline results borderline Hypothyroidism
Immunodeficiency	Consider referral to immunologist.	T-, B-, NK-cell subset analysis; Serum immunoglobulins; T-cell proliferation assays; Antibody titers to vaccinations Poor weight gain/
Failure to thrive	Eval by gastroenterology, nutrition, feeding team	Initiation of tube feeding if needed Neurologic
involvement	Neurologic exam	Assess for UMN involvement (spasticity, DTRs) LMN involvement (strength, sensation, DTRs); if abnormal consider EMG NCV.; Consider EEG if seizures are a concern.; Brain MRI if not previously performed
Musculoskeletal	Orthopedics/ physical medicine rehab/ PT OT eval	To incl assessment of:; Gross motor fine motor skills; Contractures kyphoscoliosis; Mobility, ADL, need for adaptive devices; Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)
Hearing	Audiologic eval	For sensorineural hearing loss
Speech	Speech language pathology assessment	For those w/DD /or hearing loss
Development	Developmental assessment	To incl:; Motor, adaptive, cognitive, speech-language eval; Eval for early intervention/ special education Ichthyosis/
Acanthosis	Dermatology referral if skin abnormalities	Genetic
counseling	By genetics professionals1	To inform affected persons their families re nature, MOI, implications of SPLIS to facilitate medical personal decision making Family support resources
Treatment of Manifestations in Individuals with Sphingosine Phosphate Lyase Insufficiency Syndrome Manifestation/Concern	Treatment	Considerations/Other Steroid-resistant nephrotic syndrome
Primary adrenal insufficiency	By pediatric endocrinologist	Glucocorticoid replacement; Mineralocorticoid replacement as required ± sodium supplementation; Appropriate counseling for sick days; emergency perioperative mgmt Hypothyroidism
Immunodeficiency	Care by immunologist	Monitor absolute lymphocyte count over time. If proliferation is abnormal, consider avoiding live vaccines. Most affected persons have normal or near-normal T-cell function despite absolute levels. To consider: supportive therapy (e.g., IVIG) to prevent infection based on history lab testing.
Failure to thrive	Search for underlying etiology, e.g., renal or endocrine problem.	Consider input from nutritionist, parenteral feeding.
DD/ID	See .	Neurologic
involvement	Seizure management	Rule out electrolyte disturbances hypoglycemia.; Information is insufficient re specific antiseizure mgmt.

Kisho

disorder of phospholipids, sphingolipids and fatty acids biosynthesis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

disorder of phospholipids, sphingolipids and fatty acids biosynthesis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications