Abstract Details

Title A Spontaneously Resolving Pyridostigmine Responsive Congenital Myasthenic Syndrome Caused by Isolated PREPL Deficiency

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) S45 - (-)

Poster/Presentation
Number 004

Objective

Background The hypotonia-cystinuria syndrome (HCS), caused by recessive deletions involving PREPL and SLC3A1, is characterized by cystinuria, hypotonia, ptosis, feeding problems, and growth hormone deficiency. Mutations in SLC3A1 alone cause isolated cystinuria type 1. The contribution of the defect in PREPL to HCS was not known.

Design/Methods Clinical, electrophysiology, morphology, and genetic studies in isolated PREPL deficiency and evaluation of the response of 3 HCS patients to cholinergic therapy.

Results A 3-month-old infant girl had feeding problems, fluctuating ptosis, hypotonia, and delayed motor development since birth. She inherited a novel deletion involving PREPL and SLC3A1 from her mother and a nonsense mutation in PREPL (p.M270X) from her father. Therefore the nonsense mutation in PREPL determines the phenotype. The edrophonium test was strongly positive and her muscle tone, ptosis and feeding problems improved with pyridostigmine. Microelectrode studies of anconeus endplates at age 6 months revealed reduced quantal release by nerve impulse due to decreased number of quanta available for release. The probability of quantal release was normal. The amplitude of the miniature endplate potentials (MEPP) and currents (MEPC) was reduced to [sim]40% of normal, but endplate AChR content and EM morphometry were normal for the patient's age. Over next 9 months she continued to improve and was weaned off pyridostigmine by one year of age. Because the patient has responded to pyridostigmine, we treated another infant and 2 school-age children with HCS with pyridostigmine; the infant improved temporarily, the older patients did not.

Conclusions Isolated PREPL deficiency causes a spontaneously resolving myasthenic syndrome in infancy. The defect in neuromuscular transmission is attributed to impaired quantal release by nerve impulse and the reduced MEPP amplitude.

Authors/Disclosures
Luc J. Regal, MD PRESENTER	No disclosure on file
Ettore Beghi, MD, FAAN	No disclosure on file
Duygu Selcen, MD, FAAN (Mayo Clinic)	Dr. Selcen has nothing to disclose.
Xin Ming Shen, PhD, FAAN (Mayo Clinic)	The institution of Dr. Shen has received research support from NIH. The institution of Dr. Shen has received research support from Myasthenia Gravis Foundation of American.
	No disclosure on file
	No disclosure on file
Andrew G. Engel, MD, FAAN (Mayo Clinic Rochester)	The institution of Dr. Engel has received research support from NIH.

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