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Case Reports
. 2023 Jun 12;15(1):146-152.
doi: 10.1159/000530974. eCollection 2023 Jan-Dec.

Thirty-Year Follow-Up of Early Onset Amyotrophic Lateral Sclerosis with a Pathogenic Variant in SPTLC1

Aparna Ajjarapu  1 , Shawna M E Feely  2 , Michael E Shy  3 , Christina Trout  1 , Stephan Zuchner  4 , Steven A Moore  5 , Katherine D Mathews  3   1
Affiliations
Case Reports

Thirty-Year Follow-Up of Early Onset Amyotrophic Lateral Sclerosis with a Pathogenic Variant in SPTLC1

Aparna Ajjarapu et al. Case Rep Neurol. .

Abstract

Dominant mutations in serine palmitoyltransferase long chain base subunit 1 (SPTLC1), a known cause of hereditary sensory autonomic neuropathy type 1 (HSAN1), are a recently identified cause of juvenile amyotrophic lateral sclerosis (JALS) with slow progression. We present a case of SPTLC1-associated JALS followed for 30 years. She was initially evaluated at age 22 years for upper extremity weakness. She experienced gradual decline in muscle strength with development of weakness and hyperreflexia in lower extremities and diffuse fasciculations in the upper extremities at 26 years. She lost independent ambulation at age 45 years. Pulmonary function declined from a forced vital capacity of 94% predicted at 27 years to 49% predicted at 47 years, and she was hospitalized twice for respiratory failure. To our knowledge, this is the longest documented follow-up period of JALS caused by a de novo pathogenic variant in SPTLC1.

Keywords: Case report; Juvenile amyotrophic lateral sclerosis; Neuromuscular; SPTLC1.

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Conflict of interest statement

Aparna Ajjarapu, BA, received funding from the University of Iowa Carver College of Medicine and the Paul D. Wellstone Muscular Dystrophy Specialized Research Center grant (NIH P50NS053672). Shawna M.E. Feeley, MS, LGC has no conflicts of interest. Dr. Michael E. Shy, MD receives support from NCATS and NINDS for the Inherited Neuropathies Consortium (2U54NS065712), a member of the Rare Disease Clinical Research Network (RDCRN). The INC also receives support from the Muscular Dystrophy Association (MDA) and Charcot Marie Tooth Association (CMTA). He has no other disclosures to declare that are relevant to the present manuscript. Christina Trout, RN, MSN has no conflicts of interest. Dr. Stephen Zuchner, MD, PhD has consulted for Applied Therapeutics and Dtx Pharma. He is an unpaid board member of UDN Foundation, TGP Foundation, and the advisory boards for MDA and CMTA. Dr. Steven A. Moore, MD, PhD receives funding from the Paul D. Wellstone Muscular Dystrophy Specialized Research Center Grant (NIH P50NS053672). He has nothing else to disclose. Dr. Katherine D. Mathews receives funding from the Paul D. Wellstone Muscular Dystrophy Specialized Research Center Grant (NIH P50NS053672) and the Centers for Disease Control (U01 DD001248). She serves as an advisory board member for MDA and the FSH Society; is a board member for the Friedreich Ataxia Research Alliance (FARA); receives clinical trial funding from PTC Therapeutics, Sarepta Therapeutics, Pfizer, Reata, Italfarmaco, CSL Behring, AMO Pharma, FibroGen, and Retrotope; and serves as an industry consultant for Sarepta, AskBio, ML Bio, Dyne (no personal compensation).

Figures

Fig. 1.
Fig. 1.
Pathological findings from left deltoid muscle biopsy at age 22 years. Groups of angular atrophic fibers (black arrows in panels a and c) are interspersed with normally sized to mildly hypertrophic muscle fibers. The slow myosin immunostaining (panel b) is roughly equivalent to ATPase at pH 4.3 and stains positive for type 1 muscle fibers (slow twitch). Type 1 muscle fibers are negative on fast myosin immunostaining (see, for example, muscle fibers 1a, 1b, 1c, and 1d in panel c). The fast myosin immunostaining (panel c) is roughly equivalent to ATPase at pH 9.4 and it stains positive for type 2 muscle fibers (fast twitch). Type 2 muscle fibers are negative on slow myosin immunostaining (see, for example, most of the angulated atrophic fibers in panel b). Widely scattered fibers are undergoing myonecrosis/myophagocytosis (white arrow in panel a).
Fig. 2.
Fig. 2.
Forced vital capacity by age. Not plotted here are the mean inspiratory and mean expiratory pressures. At age 45 years, for example, these pressures were 26 cm H20 and 27 cm H20, respectively.
See this image and copyright information in PMC

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