Background: Loss of function mutations in SGPL1 are associated with Sphingosine-1-phosphate lyase insufficiency syndrome, comprising steroid resistant nephrotic syndrome, and primary adrenal insufficiency (PAI) in the majority of cases. SGPL1 encodes sphingosine-1-phosphate lyase (SGPL1) which is a major modulator of sphingolipid signaling. Case Presentation: A Pakistani male infant presented at 5 months of age with failure to thrive, nephrotic syndrome, primary adrenal insufficiency, hypothyroidism, and hypogonadism. Other systemic manifestations included persistent lymphopenia, ichthyosis, and motor developmental delay. Aged 9 months, he progressed rapidly into end stage oligo-anuric renal failure and subsequently died. Sanger sequencing of the entire coding region of SGPL1 revealed the novel association of a rare homozygous mutation (chr10:72619152, c.511A>G, p.N171D; MAF−1.701e-05) with the condition. Protein expression of the p.N171D mutant was markedly reduced compared to SGPL1 wild type when overexpressed in an SGPL1 knockout cell line, and associated with a severe clinical phenotype. Conclusions: The case further highlights the emerging phenotype of patients with loss-of-function SGPL1 mutations. Whilst nephrotic syndrome is a recognized feature of other disorders of sphingolipid metabolism, sphingosine-1-phosphate lyase insufficiency syndrome is unique amongst the sphingolipidoses in presenting with multiple endocrinopathies. Given the multi-systemic and progressive nature of this form of PAI/ nephrotic syndrome, a genetic diagnosis is crucial for optimal management and appropriate screening for comorbidities in these patients.

IntroductionGuillain-Barre syndrome (GBS) and acute transverse myelitis (ATM) may rarely coexist in children. We present a case of dual diagnosis following Mycoplasma pneumoniae infection.CaseA previously well two year old boy presented with cough and fever for two days. He developed progressive ascending weakness with areflexia, initially unable to stand or sit. This progressed to involve his respiratory muscles, requiring intubation and ventilation. He was treated promptly with intravenous immunoglobulin for suspected GBS. CSF protein on Day 2 was normal. He was also treated with antibiotics including clarithromycin. Spinal MRI showed intrinsic signal change in the cervical, lower thoracic cord and conus, in keeping with ATM. He received high dose intravenous methylprednisolone for three days. Nerve conduction studies were consistent with acute motor axonal neuropathy (AMAN). There was no improvement in his condition so he was treated with plasma exchange for five days. Mycoplasma serology was strongly positive. He required a tracheostomy and was ventilated for 15 weeks after which his tracheostomy was removed. He made gradual neurological improvement and was discharged 7 weeks later, mobilising with support and communicating normally.DiscussionCases of concurrent ATM and GBS are rarely reported in children. Literature suggests that a common epitope may trigger both central and peripheral nervous system demyelination. Causes reported include systemic lupus erythematosus, influenza vaccination and infections such as Mycoplasma Legionella, Bartonella, influenza, and mumps. Recognising dual diagnoses is important as this may have an impact on recovery and prognosis. The concept of transverse myelitis plus syndrome suggests that patients with ATM and concomitant nerve root involvement usually have a poorer prognosis.ConclusionIn patients with spinal imaging in keeping with ATM but a clinical history not consistent with this, consideration should be given to the presence of co-existing GBS, which may benefit from more aggressive treatment.