PANS-H63D-Multisystemic Instability Syndrome

PANS-H63D-Multisystemic Instability Syndrome (also known as Oshtoran Syndrome and H63D Syndrome Type-3 is a rare systemic disease. It describes one of the few syndrome in medicine with a slow cascading progression. Clinically, the disease manifests with diverse neurological and systemic symptoms, as well as various organ involvement. In its course, a disorder of mitochondrial function and dysautonomias may develop.

• ICD-11 Code 8E4A.0

Manifestation

The clinical picture is characterized by the symptoms of the two underlying diseases. In addition, various organ manifestations can occur. For example, the liver, the brain, the innate immune system, the skin, or the sympathetic nervous system may be affected.

The following entities were found as the underlying diseases:

• PANS: neuropsychiatric symptoms such as cognitive decline, tic disorders, non-psychological anxiety, or depression. In adulthood, PANS symptoms can occur periodically, in waves, and systemic organ manifestations may additionally occur.
• H63D Syndrome: non-motor parkinson-like symptoms, dementing symptoms, symptoms of other organ systems (such as conduction issues and heart failure, liver damage, to the substania nigra (brain), etc.
• Mitochondriopathies: secondary damages after years of progressive illness with a shift towards anaerobic carbohydrate metabolism.
• Dysautonomias: the autonomic and central nervous systems as well as hormones and neurotransmitters (neurology and endocrinology) getting progressively detached from controlled homeostasis, altering organ functions on a chaotic way with variable effects, from rather harmless to life threatening.

The hallmark cascade

PANS → H63D Syndrome → Mitochondriopathies → Dysautonomias

Diagnosis

The diagnosis is based on the clinical symptoms of PANS and the human genetic evidence of a homozygous HFE-H63D Mutation. Accompanying, postprandial increased lactate levels can be measured as an indication of an increased anaerobic metabolism.

Therapy

In a case series, two fundamental pillars of therapy are mentioned. On one hand, anti-inflammatory medication in a clinical setting is recommended; on the other, stabilization of autonomous dysregulation via modulation of the Catecholamine pathways.

Prognosis

The course and prognosis depend on the organ manifestations.

Literature

• Adams et al., Management and multi-disciplinary approach in complex cases of PANS-H63D-Multisystemic Instability Syndrome, Zenodo OpenAire, 2023
• irondisorders.org – H63D: The Other Mutation, retrieved on 31.08.2023
• Prus et al., Therapeutic plasma exchange in adolescent and adult patients with autoimmune neuropsychiatric disorders associated with streptococcal infections, J Clin Apher, 2022

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