Dysphonia

48%

—

—

Orolingual dyskinesia

65%

—

—

Dysphagia

40%

—

—

Eye issues

Abnormal EOM

8%

—

Cognitive deficits

Impaired verbal learning executive function

Frequencynot known

Typically subtle but progress over time

Behavioral issues

Disinhibition, emotional lability, aggression

—

—

Brain MRI features

Excess brain iron accumulationon T2-weighted MRI

100%

—

Serum ferritin levels

Low serum ferritin concentrations (20 g/L) in most males postmenopausal females

82% of males; 100% postmenopausal females; 23% of premenopausal females

Typically w/in normal limits in premenopausal females EOM = extraocular muscle (function) 1. In 40 individuals with the FTL Movement disorder.

Aceruloplasminemia

AR

Early-onset movement disorder

Different MRI findings HTT

—

Huntington disease

AD

Chorea early neuropsychiatric features

Brain imaging distinguishes diagnoses. NPC1 NPC2

—

Niemann-Pick type C

AR

Early-onset movement disorder

Different MRI findings

—

PANK2

Pantothenate kinase-associated neurodegeneration (PKAN)

AR

Very similar MRI findings incl "eye of the tiger" sign

Earlier onset in PKAN

PLA2G6

Infantile neuroaxonal dystrophy (INAD) (See PLA2G6-Associated Neurodegeneration.)

AR

Imaging findings resembling but distinct from neuroferritinopathy

Earlier onset in INAD PRKN

Parkin type of early-onset Parkinson disease

AR

Early-onset movement disorder

Different MRI findings TBP

—

SCA17

AD

Chorea dystonia

Spasticity in SCA17

—

TOR1A

DYT1 early-onset isolated dystonia (DYT1)

AD

Generalized dystonia

Chorea is uncommon in DYT1 DYT1 is not assoc w/psychiatric features. Various

Mitochondrial disorders

Various

Basal ganglia abnormalities on MRI

Different MRI findings

—

VPS13A

Chorea-acanthocytosis (ChAc)

AR

Orofacial dyskinesia

Impaired reflexes in ChAc

XK

McLeod neuroacanthocytosis syndrome (MLS)

XL

Absent deep tendon reflexes in MLS AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; SCA = spinocerebellar ataxia; XL = X-linked Neurodegenerative disorders with brain iron accumulation (NBIA).

—

Treatment of Manifestations in Individuals with Neuroferritinopathy Manifestation/Concern

Treatment

Considerations/Other

Movement disorders

Levodopa, tetrabenazine, orphenadrine, benzhexol, sulpiride, diazepam, clonazepam, deanol in standard doses1

Best administered managed by mvmt disorders specialist; Response to these treatments is only seen in some persons, as mvmt disorders can be resistant to conventional therapy; no formal treatment trials have been completed.

Behavioral issues

Assessment by neuropsychiatrist/behavioral specialist

May be required for cognitive neurobehavioral features.; May require psychotropic medication to manage behavioral symptoms.

Diet/Nutrition

Ongoing dietary nutritional support

To maintain caloric intake Family/Community

Recommended Surveillance for Individuals with Neuroferritinopathy System/Concern

Evaluation

Frequency Neurologic/

movement disorders

Assessment of mvmt abnormalities

At each visit

Cognition

Eval w/neuropsychologist

Annually /or as needed

Dietary/nutritional needs

Ongoing dietary nutritional support

—

Family/Community

Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).

At each visit Iron supplements are not recommended for affected individuals and those at risk . Iron replacement therapy with careful monitoring may be required if affected individuals develop coincidental iron deficiency anemia.