# Psychological Framing of Illness: Early Family Trauma and Diagnostic Delay in Adult-Onset Metachromatic Leukodystrophy

## TL;DR

A woman's adult-onset neurological disorder was initially misdiagnosed as depression, highlighting the need for thorough evaluation in rare diseases.

## Contribution

The paper presents a case where early family trauma and psychiatric framing delayed diagnosis of adult-onset MLD.

## Key findings

- The patient's symptoms were initially attributed to psychosocial stressors rather than neurological disease.
- MRI and biochemical tests confirmed adult-onset MLD with a homozygous ARSA gene mutation.
- The case highlights the importance of integrating psychiatric and neurological evaluations in rare disease diagnosis.

## Abstract

Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive disorder of lipid metabolism characterized by deficiency of arylsulfatase A (ARSA), which leads to an accumulation of sulfatides in central and peripheral nerve system and eventually to progressive demyelination. The adult form of MLD may be misinterpreted as a psychiatric disease, since behavioral signs may precede intellectual decline. Here we report the case of a 53-year-old woman initially admitted to a psychiatric ward with symptoms of depression. The behavioral changes were initially attributed to psychosocial stressors within the family, particularly long-term emotional abuse by the patient's former partner. However, detailed anamnesis with the patient's mother revealed progressive behavioral and cognitive decline, urinary and fecal incontinence, that is, features suggestive of an underlying neurological disorder. Notably, laboratory investigations recommended 6 years earlier had not been performed. Neurological examination revealed signs of a frontal syndrome, bilateral pyramidal tract involvement, and mild polyneuropathy. Magnetic resonance imaging (MRI) demonstrated abnormal white matter signal alterations. Further diagnostic investigations showed reduced serum ARSA activity, elevated urinary sulfatides, and a homozygous pathogenic variant in the ARSA gene, confirming the diagnosis of adult-onset MLD. The homozygous mutation indicated parental consanguinity, suggesting early trauma embedded within the family. This case underscores the complexity of diagnosing MLD and emphasizes the importance of integrating psychiatric, neurological, and systemic family perspectives in the diagnostic process of rare and slowly progressing illnesses.