Vitamin C Deficiency Presenting with Progressive Gait Difficulty, Myopathy, and Movement Disorder in a Toddler

Main Document

Vitamin C is an essential water‐soluble micronutrient that is obtained exogenously through diet. Vitamin C deficiency, or scurvy, is a multisystem clinical syndrome that can present with non‐specific neurological manifestations such as non‐specific behavioral changes and motor symptoms, which can be challenging to diagnose. ¹ , ² Nutritional deficiencies should be an important consideration in children with underlying neurodevelopmental diagnoses, as well as in neurotypical children with abnormal eating habits or an increased risk of malnutrition. ³ Here we describe a unique presentation of scurvy in a child with proximal myopathy and a movement disorder in the absence of typical systemic or radiological signs.

Case Report

A previously healthy 3‐year‐old girl presented with an abnormal gait, reduced muscle bulk in lower limbs, mild spasticity, and weakness that was more prominent in the proximal muscles. Gowers's sign and hyperreflexia were also observed (Video 1). The upper‐limb examination was normal. The child has no family history of neuromuscular conditions and was the only child of nonconsanguineous parents.

Video 1.

Part 1 shows the patient while on levodopa before vitamin C supplementation. On walking, bilateral lower‐limb tremor is observed with a cautious gait. On squatting and trying to get up, proximal muscle weakness is apparent, whereas distal strength appears normal at the ankles, which demonstrated rigidity. Subtle action tremor was also observed in the hands without any dysmetria. Part 2 shows resolution of tremor and rigidity with residual hyperreflexia and subtle proximal muscle weakness.

Initial investigations, including baseline biochemistry, full nutritional screen, cerebrospinal fluid studies, and head and spine magnetic resonance imaging, were normal. A trial of levodopa (up to 4 mg/kg) for suspected dopa‐responsive dystonia was ineffective.

Over 5 months, the child became non‐ambulant and was wheelchair dependent. She developed restlessness, lower‐limb orthostatic tremor, upper‐limb postural tremor, and cogwheel rigidity in both the upper and lower limbs (not included in video). There was no diurnal variation, and tremor was absent during sleep. There was no bradykinesia.

Further investigations, including nerve conduction studies and trio whole exome sequencing, were also normal.

Upon reviewing her case again, we found that her initial vitamin studies had not been conducted due to incorrect sampling. Repeat testing due to concerns of an acquired myopathy showed severe deficiencies in both vitamin C (<5 μmol/L) and vitamin K (<0.1 nmol/L). No systemic, cutaneous, or hematological signs of scurvy and vitamin K deficiency were present. An X‐ray of her lower limbs was initially reported as normal but showed subtle radiolucent thin bands at the femoral, tibial, and fibular metaphysis upon retrospective review. A detailed dietary history then revealed a restricted diet that had worsened after an illness at age 2 years.

She was treated with 500 mg of vitamin C daily and nasogastric nutritional supplementation. Follow‐up at 2 months showed independent mobilization, full resolution of her upper and lower limb rigidity and tremor, with residual hyperreflexia and only subtle proximal muscle weakness in the lower limbs (Video 1, part 2).

Discussion

Our case highlights an atypical presentation of proximal myopathy and abnormal movements, including tremor and cogwheel rigidity in paediatric scurvy—without pain or classical systemic or radiological signs of scurvy. The complete resolution of tremor and rigidity with vitamin C replacement supports the hypothesis of vitamin C deficiency–associated basal motor nuclei dysfunction, manifesting as a movement disorder. ⁴ , ⁵

Vitamin C is essential for various biochemical processes in our body that affect our central nervous system, including hydroxylation of carnitine, biosynthesis of neurotransmitters and catecholamines, and antioxidative properties. ¹ Carnitine deficiency, along with altered levels of catecholamines, is implicated in scurvy and is thought to contribute to early neuropsychiatric and musculoskeletal symptoms. ¹ , ⁵ Gait abnormalities and refusal to walk are commonly observed in children with scurvy, which is likely attributed to pain from hemarthrosis, subperiosteal hemorrhage, and myalgia, rather than weakness. In some cases, proximal myopathy supported by the presence of Gowers's sign has also been described. ¹ , ⁶ , ⁷ Although rare, tremor has also been described as a prominent feature in both genetic and acquired myopathies, where the tremor generator is believed to be located in the sarcomere, with propagation and amplification of sarcomeric oscillatory activity through central nervous system (CNS) reflex loops. ⁸

Our patient demonstrated generalized tremor, cogwheel rigidity, and hyperreflexia that were most prominent in the lower limbs. While tremor may be partly attributed to proximal myopathy, the presence of rigidity and hyperreflexia does suggest a component of CNS dysfunction.

Acquired vitamin deficiencies or monogenic disorders affecting vitamin utilization and metabolism are implicated in movement disorders in children. ⁹ There is currently only 1 paediatric case series ¹⁰ describing an association between scurvy and infantile tremor syndrome. However, there is a close association between vitamin C deficiency and basal motor nuclei dysfunction, manifesting as a movement disorder. This has been demonstrated in rodent models as well as several case studies of parkinsonism in adults with scurvy. In these cases, the hypothesis was further supported by the resolution of symptoms with vitamin C replacement. ⁴ , ⁵

In conclusion, our case underscores the importance of considering nutritional‐reversible causes of motor and movement disorder presentation, of which vitamin C deficiency is one, even in children not thought to be in an at‐risk group. A thorough nutritional history could help expedite treatment and mitigate invasive or expensive investigations.

Author Roles

(1) Research project: A. Conception, B. Organization. C. Execution; (2) Manuscript preparation: A. Writing of the first draft, B. Review and critique.

V.H.L.N.: 1A, 1B, 1C, 2A, 2B

D.W.: 1C, 2A, 2B

C.M.: 1A, 2B

G.M.S.: 1A, 2B

R.S.: 1A, 2B

S.S.M.: 1A, 1B, 1C, 2B

Disclosures

Ethical Compliance Statement: The use of diagnostic and clinical information of patients in this study complied with the requirements of the clinical ethics committee of the John Hunter Children's Hospital. Verbal and written informed consent for use of information and videos was obtained from the patients (when adult consent was possible) or the parents of the patients for those under the age of 14 years. All authors confirm that they have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: No specific funding was received for this work, and the authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: D.W. receives funding from the Edmond J. Safra Fellowship through the Michael J. Fox Foundation.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.