Table 2.

Summary of main clinical features of patients described with genetically confirmed sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) to date (1, 2, 4–9), including our own patient.

	Patient numbers	Patient details
Total patients	35 (+ 4 fetal demise)	Initial presentation at ages varying postnatally to 19 years
Sex (M:F)	21:14
Deaths	15	Age at demise varying postnatally, with fetal hydrops, to 9 years; several precipitated by septic episodes
Nephrotic syndrome	29	Congenital to oldest presentation at 19 years with SRNS, with 19 patients presenting in infancy, six patients were reported to have renal transplantation (two of these required a second transplant).
Adrenal insufficiency	23* (five additional cases with adrenal calcification on imaging)	Glucocorticoid deficiency in all cases ± mineralocorticoid deficiency. Age at presentation varying from early postnatal to oldest at 11 years, 11 patients presenting in infancy. 11 patients noted to have adrenal calcifications on imaging.
Hypothyroidism	12	Primary hypothyroidism with mildly raised TSH levels in all cases where biochemistry was reported
Gonadal dysfunction	7	Male patients presenting postnatally with cryptorchidism ± microphallus, all with raised gonadotrophins indicating primary gonadal failure.
Ichthyosis	12
Neurological/ Developmental delay	18	Phenotypically heterogenous, varying from microcephaly, seizures, sensorineural deafness to later presentation with abnormal gait, peripheral neuropathy, progressive neurological deficit. Central and peripheral nervous system pathology variably reported. Neuroimaging findings varied from corpus callosum atrophy, cortical atrophy, cerebellar hypoplasia to basal ganglia involvement.
Immunodeficiency	13	Most consistently this is an absolute lymphopenia, some patients additionally with hypogammaglobulinemia and neutropenia.
Other features	<5 patients	Dysmorphic features, skeletal abnormalities, liver dysfunction are reported.

^*Indicates biochemically proven.