The case of a patient with MIRAGE syndrome with familial dysautonomia-like symptoms

Yuki Kawashima-Sonoyama; Keisuke Okuno; Tomotsune Dohmoto; Kanako Tanase-Nakao; Satoshi Narumi; Noriyuki Namba

doi:10.1038/s41439-021-00158-6

The case of a patient with MIRAGE syndrome with familial dysautonomia-like symptoms

Human Genome Variation ◽

10.1038/s41439-021-00158-6 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Yuki Kawashima-Sonoyama ◽

Keisuke Okuno ◽

Tomotsune Dohmoto ◽

Kanako Tanase-Nakao ◽

Satoshi Narumi ◽

...

Keyword(s):

Familial Dysautonomia ◽

Catecholamine Metabolites ◽

Adrenal Hypoplasia ◽

Functional Analyses

AbstractWe describe a case of posthumously diagnosed MIRAGE syndrome (Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital problems, and Enteropathy) in a girl with a new pathogenic SAMD9 variant (p.F437S), who was initially considered to have familial dysautonomia (FD)-like disease due to increased levels of catecholamine metabolites. Functional analyses of F437S-SAMD9 were performed, showing characteristics of disease-causing variants. This new SAMD9 variant (p.F437S) also causes MIRAGE syndrome.

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EXCRETION OF CATECHOLAMINE METABOLITES BY CHILDREN WITH FAMILIAL DYSAUTONOMIA

PEDIATRICS ◽

10.1542/peds.46.4.513 ◽

1970 ◽

Vol 46 (4) ◽

pp. 513-522

Author(s):

Stanley E. Gitlow ◽

Laura M. Bertani ◽

Elizabeth Wilk ◽

Biao Lan Li ◽

Stanley Dziedzic

Keyword(s):

Homovanillic Acid ◽

Matched Control ◽

Normal Subjects ◽

Biochemical Parameter ◽

Familial Dysautonomia ◽

Catecholamine Metabolism ◽

Vanillylmandelic Acid ◽

Sensitive Assay ◽

Specific Nature ◽

Catecholamine Metabolites

Although a defect in catecholamine metabolism has been suggested in familial dysautonomia, the specific nature and extent of this abnormality has not been defined. Highly specific and sensitive assay techniques were used to measure the excretion of vanillylmandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (HMPG), total metanephrines (TM), normetanephrine (NM), and homovanillic acid (HVA) of 52 dysautonomic patients and 180 normal subjects. Twenty parents of dysautonomic patients and age-matched control subjects were studied similarly. Patients with familial dysautonomia were found to excrete elevated quantities of HVA, diminished quantities of VMA and HMPG, and normal amounts of TM and NM in comparison with normal subjects. The excretion of the sum of the deaminated catecholamine metabolites proved to be more aberrant in familial dysautonomia than any other biochemical parameter measured. The findings of this study are more compatible with an abnormality in catecholamine synthesis rather than in release. Parents of dysautonomic subjects excreted normal amounts of vanillylmandelic acid and homovanillic acid.

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