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. 2025 May;48(3):e70038.
doi: 10.1002/jimd.70038.

Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature Review

Maria-Rita Moio  1 , Julia Cordeiro Milke  2 , Yannick Moutapam-Ngamby-Adriaansen  1   3 , Arthur Minas Alberti  4   5 , Marie Gernay  6 , Eduardo Augusto Schütz  5   7 , Ida Vanessa Doederlein Schwartz  5   7   8 , François Maillot  1   3   9
Affiliations

Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature Review

Maria-Rita Moio et al. J Inherit Metab Dis. 2025 May.

Abstract

Inherited metabolic diseases (IMDs) are genetic disorders that disrupt biochemical processes in the human body, due to pathogenic variants in genes encoding enzymes or transporters. While IMDs are mostly diagnosed in infancy or childhood, there is an increasing number of diagnoses in adult patients. Delayed diagnosis, particularly in older patients, may reflect the diagnostic odyssey usually observed in rare diseases' patients and can result in complications and reduced quality of life for patients and their families. The aim of the study was to better characterize the diagnosis of IMDs in older patients (≥ 65 years). We conducted a systematic literature review (SLR) to examine the diagnosis and clinical presentation of IMDs in patients aged 65 and older. We searched databases like PubMed, Embase, and Lilacs for relevant studies from 1965 to 2023. A total of 260 articles were included, representing 293 patients with a median age of 69 years at diagnosis. From this SLR, 67 different diagnoses have been reported. The most frequently reported diseases were Fabry disease, alkaptonuria, Gaucher disease, mitochondrial disorders, and glycogen storage disease type V. Median diagnostic delay was 14.5 years with a wide range of 1-91 years. Musculoskeletal symptoms were the most frequently reported, followed by neurological and cardiovascular symptoms. Our findings underscore the importance of recognizing IMDs in older patients and the need for awareness among healthcare providers to improve diagnosis and patient care. Future guidelines and teaching programs should incorporate metabolic investigations for older patients presenting with symptoms suggestive of IMDs.

Keywords: adult metabolic medicine; elderly; inborn errors of metabolism; inherited metabolic disease; older patients.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the study selection process.
FIGURE 2
FIGURE 2
Frequency of the first, second, third and fourth symptoms reported by the patients included in the systematic review. Rank 1: First reported symptom; 2: Second reported symptom; 3: Third reported symptom; 4: Fourth reported symptom.
FIGURE 3
FIGURE 3
Relations between the first and the second symptoms reported by the patients included in the SLR.
FIGURE 4
FIGURE 4
Clinical picture of older patients diagnosed with Fabry disease (n = 66).
See this image and copyright information in PMC

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